Molecules 2011, 16, 2146-2190; doi:10.3390/molecules16032146 
 

 

molecules 
ISSN 1420-3049 

www.mdpi.com/journal/molecules 
Review 

Antiplasmodial Natural Products 

Cláudio R. Nogueira and Lucia M. X. Lopes * 

Instituto de Química, Universidade Estadual Paulista, UNESP, C. P. 355, 14801-970, Araraquara, SP, 

Brazil; E-Mail: nogueiracr@rocketmail.com (C.R.N.) 

*  Author to whom correspondence should be addressed; lopesxl@iq.unesp.br;  

Tel.: +55-16-33019663; Fax: +55-16-33019692.  

Received: 25 January 2011; in revised form: 15 February 2011 / Accepted: 2 March 2011 /  

Published: 4 March 2011 

 

Abstract: Malaria is a human infectious disease that is caused by four species of 

Plasmodium. It is responsible for more than 1 million deaths per year. Natural products 

contain a great variety of chemical structures and have been screened for antiplasmodial 

activity as potential sources of new antimalarial drugs. This review highlights studies on 

natural products with antimalarial and antiplasmodial activity reported in the literature 

from January 2009 to November 2010. A total of 360 antiplasmodial natural products 

comprised of terpenes, including iridoids, sesquiterpenes, diterpenes, terpenoid 

benzoquinones, steroids, quassinoids, limonoids, curcubitacins, and lanostanes; flavonoids; 

alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; polyketides, including 

halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; 

benzophenones; macrolides; and miscellaneous compounds, including halogenated 

compounds and chromenes are listed in this review. 

Keywords: malaria; antimalarial; antiplasmodial; Plasmodium 

 

1. Introduction 

Malaria is an infectious disease caused by four protozoan species of the genus Plasmodium 

(Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax) [1]. 

Small human infection outbreaks caused by a malaria parasite of monkeys, Plasmodium knowlesi, have 

also been reported in Southeast Asia [2]. The majority of the cases of malaria and deaths (malaria kills 

1-2 million people each year) are caused by P. falciparum. P. vivax is generally considered less 

OPEN ACCESS



Molecules 2011, 16                            

 

 

2147

dangerous than P. falciparum, although both can cause deadly complications in infected people. 

Nearly 3 billion people are at risk of infection with the malaria parasite P. vivax. A new map of areas 

where this parasite has been reported, including risk areas, has been drawn [3]. These grim statistics 

could become even worse if resistance to the existing antimalarial drugs develops further [4]. 

According to WHO [5], the elimination of malaria from countries with high transmission rates is a 

long-term goal that will depend on the success of research and development to deliver a more robust 

arsenal of tools than those available today – tools of greater potency and effectiveness, especially those 

with an impact on transmission, and replacements for medicines and insecticides that are being lost to 

resistance. The growing resistance to existing antimalarial drugs could nullify efforts to eliminate this 

deadly disease. Unfortunately, there are still very few drugs that are active against malaria (artemisinin, 

atovaquone, and chloroquine analogues) [4, 6] and vaccines against malaria are not yet available [6].  

At present, drug resistance of the malaria parasite is widespread, no new chemical class of 

antimalarials has been introduced into clinical practice since 1996, and there has recently been an 

increase in parasite strains with reduced sensitivity to the newest drugs [7]. Meanwhile, recent 

advances in genome-based technologies and in vitro screening of whole parasites and a great number 

of compounds (natural and synthetic) have broadened the range of therapeutic targets and are accelerating 

the development of a new generation of treatments for both the control and eradication of malaria [6]. 

Several excellent reviews on antiplasmodial compounds, including natural products, have been 

published in recent years [8-18]. Thousands of chemicals have been assayed for antiplasmodial 

activity, such as those described by Gamo et al. [7].  

The current review provides an overview of a great number of bioactive natural products that have 

recently been described in the literature (from January 2009 to November 2010) as showing 

antiplasmodial activity (in vitro), along with a few compounds that were tested for antimalarial activity 

in animal models [19] using Plasmodium knowlesi (in simians), Plasmodium yoelii, Plasmodium 

berghei, Plasmodium chabaudi (in mice), and Plasmodium gallinaceum (in birds). In most of these 

bioassays, antiplasmodial activities were assessed using different P. falciparum strains, which include 

chloroquine-sensitive (NF54, NF54/64, 3D7, D6, F32, D10, HB3, FCC1-HN, Ghana, MRC-02, TM4), 

chloroquine-resistant (BHz26/86, Dd2, EN36, ENT30, FcB1, FCM29, FCR3, FCR-3/A2, FCR3F86, S20, 

W2,), chloroquine-resistant and pyrimethamine-resistant (K1, TM91C235), pyrimethamine-resistant 

(HB3), cycloguanil-resistant (CDC1), and chloroquine- and antifolate-resistant (K1CB1). Most of 

evaluations used the [3H]-hypoxanthine-incorporation assay to assess parasite inhibition of growth in 

the presence of the test-drugs. Antimalarial activity of new compounds has also been determined by 

using: i) the fluorometric method based on the intercalation of the fluorochrome PicoGreen (SYBR) in 

the parasite DNA, [20]; ii) enzyme-linked immunosorbent assays (ELISAs) with monoclonal 

antibodies, which measure the P. falciparum-specific antigen histidine-rich protein 2 (HRP2) or lactate 

dehydrogenase protein (pLDH). A chemical reaction using ferriprotoporphyrine biocrystallization 

(FBTI Inhibition Test) has been used to provide a possible action mechanism for presumed 

antimalarial compounds [21]. Protein farnesyltransferase (FTase) bioassays have also been used to 

provide insight into their mode of action against P. falciparum [22]. The effects of natural products on 

glutathione (GSH), which plays a key role in redox mechanisms, and on cysteine (Cys), which is one 

of the substrates needed for the de novo synthesis of P. falciparum GSH, as well as their impact on  

β-hematin formation have been investigated, since GSH participates in heme detoxification [23]. The 



Molecules 2011, 16                            

 

 

2148

advantages and disadvantages of the different in vitro screening methods have been discussed by 

Krettli et al. [24] and Wein et al. [25]. For in vivo bioassays P. berghei and P. chabaudi chabaudi have 

been used most often. The cytotoxicities of the active compounds compiled in this review have 

generally been evaluated in HEK293, Vero or HeLa cells. For the details of the methodologies, see the 

appropriate references cited herein.  

Several criteria have been proposed for considering a compound as active. Generally, a compound is 

considered to be inactive when it shows an IC50 > 200 μM, whereas those with an IC50 of 100-200 μM 

have low activity; IC50 of 20-100 μM, moderate activity; IC50 of 1-20 μM good activity; and IC50 < 1 μM 

excellent/potent antiplasmodial activity [12]. In this review, regardless of the in vitro or in vivo method 

adopted for antiplasmodial or antimalarial evaluation, we list the active and moderately active 

compounds in accordance with the corresponding cited literature (data for inactive compounds are not 

shown in this review). 

A total of 360 antiplasmodial natural products comprised of terpenes, including iridoids, 

sesquiterpenes, diterpenes, terpenoid benzoquinones, steroids, quassinoids, limonoids, curcubitacins, 

and lanostanes; flavonoids; alkaloids; peptides; phenylalkanoids; xanthones; naphthopyrones; 

polyketides, including halenaquinones, peroxides, polyacetylenes, and resorcylic acids; depsidones; 

benzophenones; macrolides; and miscellaneous compounds, including halogenated compounds and 

chromenes are listed in this compilation (Figures 1-44). 

2. Terpenes 

2.1. Iridoids and halogenated monoterpenes 

Phenylpropanoid conjugated iridoids 1-5 (Figure 1) have been isolated from Morinda morindoides 

(Rubiaceae). All of these compounds except for 3 potently inhibited parasite proliferation (P. 

falciparum strain CDC1, IC50 values of 0.04 to 4.1 µM) with little cytotoxicity against the host 

mammalian cells (KB 3-1) [26]. The iridoid swertiamarin (6) has been obtained from Enicostemma 

littorale (Gentianaceae) and showed promising results in vitro in a schizont maturation inhibition 

assay, with an IC50 value of 44.4µ [27].  

Figure 1. Structures of iridoids and halogenated monoterpenes 1-9. 

 R1 R2 R3 R4 

1 Ac OMe H OH

2 Ac H H OH

3 H OMe H OH

4 H H H OH

5 H OMe      =O                

O
O

O

CO 2Me

H

H

O O
OH

OH
OH
OR

1

R
3

OH

R
2

R
4

O

O

O

OH

OGlc
H

6

Cl

CHO

Cl

Cl

8

Cl Cl

ClCl
Cl

7

Cl

ClCl
Cl

9
 



Molecules 2011, 16                            

 

 

2149

Halogenated monoterpenes 7-9 with a 3,7-dimethyl-3,4-dichloro-octa-1,5,7-triene skeleton obtained 

from the marine red alga Plocamium cornutum (Plocamiaceae) exhibited antiplasmodial activity 

toward a chloroquine-sensitive strain of P. falciparum. Those bearing a 7-dichloromethyl substituent 

showed higher activity, with IC50 values ranging from 16 to 27 μM. 

2.2. Sesquiterpenes 

The eremophilane sesquiterpenoids berkleasmins A (10) and C (11) (Figure 2), obtained from the 

saprobic fungus Berkleasminum nigroapicale, showed antiplasmodial activity with IC50 values of 6.0 

and 5.4 µ, respectively [29]. The sesquiterpene lactones vernaguline A and B, vernodalol, and 

vernodalin (12-15) were isolated from Distephanus angulifolius (Asteraceae), and while they exhibited 

antiplasmodial activity against chloroquine-sensitive (D10) and chloroquine-resistant (W2) P. 

falciparum strains (IC50 values of 1.5 to 4.9 μM), they also exhibited cytotoxicity in a hamster ovarian 

cell line [30]. 
 

Figure 2. Structures of sesquiterpenes 10-17. 

 

O
OH

H

O
O

OOH

OH

10 11

O
OH

O

OOH

OH
O

12

H O

O

O
O

O

OH

O

O

H O

O

O
O

O

OH

O

O

13 14

O
O

OH

O

OH

O

O

H
O

O
O

O

OH

H
O

O

O
15

16

O
O

H
O

OH

H

17

O

O

O

O

 
 

Okundoperoxide (16) was isolated by the bioassay-guided fractionation of extracts from Scleria 

striatinux (syn. S. striatonux, Cyperaceae). This compound contains a cyclic endoperoxide structural 

moiety and showed antiplasmodial activity against W2 and D6 (IC50 ~1.8 µ), K1 (IC50 = 5.6 µ), 

and NF54 (IC50 = 4.9 µ) [31]. 

Studies on the Carpesium genus (Compositae) suggest that the antiplasmodial activity against P. 

falciparum is due to the presence of 11(13)-dehydroivaxillin (17) in the EtOAc extracts of C. cernuum. The 

antimalarial activity of 17 was evaluated against P. berghei in mice. Its LD50 was determined to be  



Molecules 2011, 16                            

 

 

2150

51.2 mg/kg, while doses of 124 mg/kg and above were found to be lethal to mice.  

DDV (2, 5, 10 mg/kg/day) exhibited a significant blood schizonticidal activity in 4-day early infection, 

repository evaluation and in an established infection with a significant mean survival time comparable to 

that of the standard drug (chloroquine, 5 mg/kg/day) [32]. 

 

Figure 3. Structures of sesquiterpenes 18-46. 
 

O

O
O

OH

H

O

O

H
H

O

33           

O

O

O

O

31          

O

O

H

O
H

32          

O

O

O

30         

34          

O

O
O

OH

H

O

H
H

O

O

O

O
O

AcO

H

35          

O
O

36          

O
O

O

37          

O

OR
2
O R

3

HR
1
O

 R1 R2 R3

23 Ac H H

24 H H H

25 H tig OH

26 H H Otig

27 Ac Ac H

28 Ac H OAc            

O

OOH

HAcO

OAc

29           

O

OO RO

H

 R1

18 Ac

19 i-but

20 i-val              

O

OO RO

H

 R1

21 H

22 i-val              

 
 

 

 

 

 



Molecules 2011, 16                            

 

 

2151

Figure 3. Cont. 

 

O

O

O

O
O

RO

 R

41 H

42 Ac              

O

O

O

O

OH
OH

OH

40          

O

R

H

O

R
1

 R R1

38 H OH

39 OH H            

O

O

O

O O
O

R

 R

43 OH

44 OAc              

O

O

O

O
O

OH

OAc

45          46           

O

O

O

 
 

In tests of 33 sesquiterpene lactones from several genera, including Arnica, Xanthium, and Inula 

(Asteraceae), Schmidt et al. [33] found that the antiprotozoal activities were significantly correlated 

with cytotoxicity, and the major determinants of this activity were α,β-unsaturated structural elements. 

Among the tested sesquiterpene lactones, 29 (compounds 18-46, Figure 3) showed activity against P. 

falciparum (K1) with IC50 values of 0.3 to 27.5 µM [33].  

2.3. Diterpenes 

Aberrarone A (47, Figure 4) is a natural product from the Caribbean sea whip Pseudopterogorgia 

elisabethae (Gorgoniidae). This compound, together with colombiasin A (48), showed in vitro activity 

against a chloroquine-resistant strain of P. falciparum (W2, IC50 values of 30.3 and 31.8 μM, 

respectively) with the use of a fluorometric method (PicoGreen) [34].  

 

Figure 4. Structures of diterpenes 47 and 48. 
 

O
O

H
H

O

O

H
47         48         

O

O

OH

H

H

 



Molecules 2011, 16                            

 

 

2152

The dolabellanes 49-63 (Figure 5) and dolastane 64 from a Eunicea species Caribbean octocoral 

(Gorgoniidae) were tested for their inhibitory activity toward the growth of P. falciparum (W2). These 

compounds were active with IC50 values of 9.4 to 59.6 μM [35]. 

 

Figure 5. Structures of dolabellanes 49-63. 

 

O

H

O O

H

O

OAc

H

O

HOO
H

O

OAc

O

H

49 50 51 52

H

OO

H
O

H

H

O

HOO

H

HOO

O

H

O

53 54 55 56

H

O

H
O

H

OH

57 58

H

O

OH

H

64

H

O

OR

 R

59 H

60 Ac            

H

OO

H
R

1

R

 R R1

61 H H

62 OAc H 

63 H OAc      

 

Gomphostenin clerodane diterpenes 65 and 66 (Figure 6) obtained from Gomphostemma niveum 

(Lamiaceae) were tested against P. berghei in mice and produced a dose-dependent chemo-suppression 

effect. Diterpene 65 exhibited the highest percent of chemo-suppression, i.e. 92.65% at a dose of  

200 mg/kg/day. In a curative test, the survival period of the infected mice was significantly prolonged at 

200 mg/kg dose of 66 [36]. Gomphostenin (65) and Gomphostenin-A (66) exhibited in vitro 

antiplasmodial activities against the MRC-02 strain of P. falciparum with IC50 values of 114.9 and  

9.8 µM, respectively [37]. In contrast, the antiplasmodial activity of ent-kaur-16-en-19-oic acid (67) 

from Schefflera umbellifera (Araliaceae) against the chloroquine-susceptible strain D10  

(IC50 = 106.5 µM) was not very significant [38]. 



Molecules 2011, 16                            

 

 

2153

Figure 6. Structures of clerodane and kaurane diterpenes 65-67. 

H

CO2H

67         

O
H

OR

OO

 R

65 H

66 Ac            
 

 

2.4. Nitrogenated diterpenes 

Isonitrile diterpenes 68-71 (Figure 7) of the amphilectane family have been isolated from the 

sponge Ciocalapata sp. (Halichondriidae). They exhibited strong activities against P. falciparum (K1) 

with IC50 values of 0.09 to 1.07 µM. Except for 8,15-diisocyano-11(20)-amphilectene (68), which was 

cytotoxic against both MCF-7 and fibroblast cell lines, these diterpenes showed no significant 

cytotoxicity against either of the targeted cell lines [39]. Alkaloid 72 is also a formamide and isonitrile, 

diterpene that was isolated from the tropical marine sponge Cymbastela hooperi (Axinellidae). In in 

vitro antiplasmodial bioassays using three strains (FCR3F86, W2, and D6) of the malaria parasite  

P. falciparum, 72 was found to have good activity (IC50 = 1.5 µM), whereas the corresponding  

di-formamide derivative 73 showed only moderate activity (IC50 = 41.0 µM) [40]. 

 

Figure 7. Structures of nitrogenated diterpenes 68-73. 

 

CN

H

HH NC
NC

H

HH

H

HH NC

H

HH NC

68         69         70         71

H

HH

H

H

H

NH

R

H

O

 R

72 NC

73 NHCHO       
 

 

2.5. Tetranorditerpenes  

Tetranorditerpenoid dilactones 74-81 and an oidiolactone 82 (Figure 8), isolated from the fungus 

Sclerotinia homoeocarpa, exhibited excellent to good antiplasmodial activity (IC50 values of 0.1 to  

8.0 µM). However, they also showed high cytotoxicity, which preclude their use as potential 

antimalarial agents [41]. 

 



Molecules 2011, 16                            

 

 

2154

Figure 8. Structures of tetranorditerpenes 74-82. 

 R

74 H

75     OH

 R

77 H

78     OH

76  R     R1

79 H    OH

80     OH   H

81      H     H

O

O

O

O
O

R

O

O

O
O

R

O

O

O
O

R
1

R
O

O

O

O
O

OH
O

O

OH

CO2H

82

 

2.6. Terpenoid benzoquinones and analogues 

 

Terpenoid benzoquinones and analogues 83-89 (Figure 9) isolated from the root extract of Cordia 

globifera (Boraginaceae) exhibited antiplasmodial activity against the P. falciparum strain K1 with 

IC50 values of 0.8 to 13.9 μM. The antifungal and cytotoxic activities of these compounds were also 

evaluated [42]. 

 

Figure 9. Structures of terpenoid benzoquinones and analogues 83-89. 

 
O

O

OH

OH

CHO

83           

O

O
H

O

O
H

84           85           

88           

O

OH

CHO

89

OR

OR
H

 R

86 H

87 Ac         

 

2.7. Steroids 

The major steroid 90 together with three other steroids 91-93 (Figure 10) isolated from the marine 

sponge Callyspongia fibrosa (Callyspongiidae) showed antiplasmodial activity (P. falciparum strains 

3D7 and K1 with IC50 values of 20.5 to 54.8 µM). Parasite growth was assessed as pLDH activity and 

90 exhibited better activity against a chloroquine-resistant strain of P. falciparum than on a 

chloroquine-sensitive strain [43]. Two steroidal peroxides 94 and 95 from another marine sponge 



Molecules 2011, 16                            

 

 

2155

Ciocalapata sp. (Halichondriidae) showed antiplasmodial activity against P. falciparum K1  

(IC50 values of 6.28 and 7.13 µM, respectively), and cytotoxicity against human cells in a breast cancer 

cell line MCF-7 (IC50 values of 0.025 and 0.003 µM, respectively), with very little toxicity against 

human fibroblasts [39]. 

An evaluation of the effects of four steroid derivatives 96-99 and a sapogenin 100 extracted from 

Solanum nudum (Solanaceae) on the total glutathione (GSH) and cysteine contents in P. falciparum in 

vitro showed that 96 increased total glutathione and cysteine concentrations while 99 decreased the 

concentrations of both thiols. Acetylation at C16 was crucial for the effect of 96 while type furostanol 

and terminal glucosidation were necessary for the inhibitory properties of 99. The combination of 

steroids and buthionine sulfoximine, a specific inhibitor of a step-limiting enzyme in GSH synthesis, 

did not modify the glutathione contents. In addition, 96 inhibited more than 80% of  

β-hematin formation at 5.0 mM, while the other steroids did not show any effect [23]. 

 

Figure 10. Structures of steroids 90-100. 

 

OH

OH

OAc

R

H

R
1

OH

OH
OH

H

OH

 R R1

90 OH H

91 H H

92 OH OH                                  

93

OH

H

H

O
O

94

OH

O O O

95

O

O

R
2

R
1

 R1 R2

96 OAc OH

97 OH OH

98 OAc OGlu           

O

OH

OGlu
O

O

O

O

99 100
 

2.8. Quassinoids 

Delaumonones A (101) and B (102) (Figure 11) have been isolated from the bark of Laumoniera 

bruceadelpha (Simaroubaceae). These quassinoids showed antiplasmodial activity against the P. 

falciparum strain 3D7 (IC50 values of 0.6 and 1.2 µM, respectively) and cytotoxicity against HL-60 

cells (IC50 101: 3.1 µM; 102: 4.6 µM). Another isolated quassinoid, the isobrucein A (103)  

(IC50 = 0.05 µM), was more active than delaumonones A and B, but it also showed a potent 



Molecules 2011, 16                            

 

 

2156

cytotoxicity against HL-60 cells (IC50 = 0.01 µM) [44]. The tea of young leaf of Quassia amara 

(Simaroubaceae) also contains several quassinoids 104-111, including simalikalactone D (104) and 

simalikalactone E (105) [45, 46]. These quassinoids inhibited the growth of P. falciparum cultured in 

vitro (with IC50 values of 1 to 420 nM), independently of the strain sensitivity to chloroquine. 

Compound 105 decreased gametocytemia with an IC50 value seven-fold lower than that of primaquine, 

and was also less toxic than simalikalactone D (104) when tested on nontumorogenic cells. In vivo, 

105 inhibited murine malaria growth of P. vinckei petteri by 50% at 1 and 0.5 mg/kg of body 

weight/day, by the oral or intraperitoneal routes, respectively [45, 46]. 

 

Figure 11. Structures of quassinoids 101-111. 

O

O

O

O

O

R

OOH

OH
OH

H H

H

H

O

O

O

O

O

O

OMe

OOH

OH
OH

H H

H

H

O

O

O

O

O

O

OH

OH
OH

H H

H

H

O

 R

101 OH

103 OMe     

102 104

O

OH

O

OMe

O
O

H H

H

H

O

MeO

O

OMe

O
O

H H

H

H

O

MeO

OH

OMe

O
O

H H

H

H

106 107 108

O

O

O

O

O

OH

OH
OH

H H

H H

O
O

O

O

MeO

O

OMe

O
O

H H

H

H

105

109

O

MeO

O

OMe

O
O

H H

H

H

OH O

MeO

O

OMe

O
O

H H

H

H

OH

110 111
 

2.9. Limonoids 

 

In vitro antiplasmodial tests using the D10 and W2 strains of P. falciparum showed that gedunin 

(112), azadirone (113), and neemfruitin A (114) had significant activity, and limonoids 115-121 from 

Azadirachta indica (Meliaceae) had a good activity (IC50 values of 1.2 to 10.0 µM) (Figure 12) [47]. 

 

 

 



Molecules 2011, 16                            

 

 

2157

Figure 12. Structures of limonoids 112-121. 

 R

113 H

115 =O

 R

112 OAc

117 OH

O

H

H

OAc

O

R

O

H

R

O

O
O

H

O

116

O

H

H

OAc

O

O

O

O

H

H

OAc

O

OH

OAc

H

114

O

H

H

OAc

O

OH

H

O

H

H

OAc

H

O
OHH

OH

118 119

O

H

H

OAc

O
H

OH
OH

OH

120

O

H

H

OH

H

O
H O

AcO

H

H

121
 

Figure 13. Structures of cucurbitacins 122-134. 

OH

H

O

H

OH

O

OH

H

O

H
OH

124122

OH

H

O

H

OH

O

123

OH

H

R
1

H

R
2

R
R

3

 R R1 R2 R3

125 OH OH OH H

126 OMe OH OH H

127 OMe OGlu H H

128 OH OMe H OH

129 OH OH H H

130 OH OH  H OH

OH

H

OH

H

OH

OH

OH

131

OH

H H
OH

O

132

OH

H

R

H

OH

OH

 R

133 OH

134 OMe  

 
 



Molecules 2011, 16                            

 

 

2158

2.10. Cucurbitacins 

 

Thirteen cucurbitane-type triterpenes 122-134 (Figure 13) have been isolated from Momordica 

balsamina (Curcubitaceae) and have been shown to exhibit antiplasmodial activity against the P. 

falciparum chloroquine-sensitive strain 3D7 and the chloroquine-resistant strain Dd2. Triterpenes 130 

and 133 had the highest antiplasmodial effects against both strains (IC50 130: 4.6 and 133: 7.4 μM, 

3D7; 130: 4.0 and 133: 8.2 μM, Dd2). Furthermore, a preliminary evaluation of the toxicity of 

compounds 122-126 and 130 toward human cells in a breast cancer cell line (MCF-7) showed that 

these triterpenes were inactive or showed only weak toxicity (IC50 values >19.0 μM) [48]. 

2.11. Lanostanes 

Ethyl acetate extract of the mushroom Ganoderma lucidum (Polyporaceae) yielded six lanostanes 

135-140 (Figure 14). These lanostanes exhibited in vitro antiplasmodial activity with IC50 values of  

6 to 20 μM [49]. Another lanostane, garcihombronane D (141), from Garcinia cymosa (Clusiaceae) 

showed a selective activity against P. falciparum (IC50 7.7 µM) [50]. 

 

Figure 14. Structures of lanostanes 135-141. 

 

O
OH

CO2H

137
O

OH

R

 R

135 CO2H

136 CHO   

R
1

CO2HR

 R R1

138 H =O

139 OH OH   
 

O

CO2H

OH

141

O

OH

OH

140
 

 

2.12. Other triterpenes 

 

The triterpene 3-hydroxy-glutin-5-ene, which was also isolated from Garcinia cymosa (142) 

(Figure 15), showed activity against P. falciparum (IC50 31.0 µM) and a cytotoxicity of 6.9 µM toward 

MRC-5 cells [50]. Hop-17(21)-en-6R,12-diol (143) was isolated from the scale insect pathogenic 

fungus Aschersonia paraphysata. It exhibited antiplasmodial activity with an IC50 value of 15 μM [51]. 

Tingenin B, (22- hydroxytingenone) (144), has been isolated as the main antibacterial constituent 

from Elaeodendron schlechteranum (Celastraceae). It was active against T. cruzi (IC50 < 0.6 μM),  

T. brucei (IC50 < 0.6 μM), L. infantum (IC50 = 1.2 μM), and P. falciparum (IC50 = 0.8 μM). Tingenin B 

was highly cytotoxic to MRC-5 cells (CC50 1.0 μM), which indicates poor selectivity [52]. Betulin 



Molecules 2011, 16                            

 

 

2159

(145) has been isolated from Schefflera umbellifera (Araliaceae), and exhibited good antiplasmodial 

activity (IC50 = 7.2 μM) against a chloroquine-susceptible strain (D10) [38]. Betulinic acid (146) 

showed antiplasmodial activity against chloroquine-resistant P. falciparum parasites (W2 strain, 

chloroquine-resistant and mefloquine sensitive) in vitro, with an IC50 value of 9.9 μM [53]. 

 

Figure 15. Structures of terpenes 142-146. 
 

CO2H

OH

142

H

H

H

OH

OH
143

OH

O

OH

O

144

 R R1

145 H CH2OH 

146 H CO2H      

R
1

RO

 
 
3. Flavonoids 

 

Flavonoids 147 and 148 have been isolated from Neoraputia magnifica (Rutaceae). These 

flavonoids, together with 149 (Figure 16), isolated from Lonchocarpus subglaucescens (Leguminosae), 

exhibited antiplasmodial activity against the P. falciparum strain 3D7 with IC50 values of 7.6, 6.9, and 

9.5 µM, respectively [54]. The luteolin 7-O--D-glucopyranoside 150 also showed antiplasmodial 

activity (IC50 = 4.9 M for the D6 strain and 4.0 M for the W2 strain), and this compound did not 

exhibit cytotoxicity in Vero cells up to a concentration of 10.6 M [55]. 

The flavone 3-methoxycarpachromene (151) isolated from Pistacia atlantica (Anacardiaceae) 

showed an IC50 value of 3.4 µM toward the P. falciparum strain K1 [56], whereas dalparvone (152) 

from the stems of Dalbergia parviflora (Leguminosae) exhibited moderate antimalarial activity with 

an IC50 value of 24.8 μM [57]. 

The in vitro antiplasmodial activities of the main hop chalcone xanthohumol (153) and seven of its 

derivatives were evaluated against two strains of P. falciparum (poW, Dd2). Xanthohumol had the 

highest activity, with IC50 values of 8.2 (poW) and 24.0 M (Dd2) [58].  

 Compounds obtained from Morinda morindoides (Rubiaceae) were evaluated in vitro for 

antiplasmodial activity against a Congolese chloroquine-sensitive strain of P. falciparum. Quercetin 

(154) exhibited good antiplasmodial activity with an IC50 value of 19.2 , whereas alizarin and 

chrysazin displayed only moderate activity (58.3 < IC50 < 124.9 M) [59].  

The isoflavanone 155 has been isolated from Ormocarpum kirkii (Papilionaceae) and has been 

shown to have antiplasmodial activity with an IC50 value of 23.7 μM [60]. 

 



Molecules 2011, 16                            

 

 

2160

Figure 16. Structures of flavonoids 147-155. 
 

OMe

O

O

O

O
O

O O

OOH

OH

OMe

O

O

OH

OH

OH

OMe

OMe

O

O

MeO

OMe

O
O

OMe

O

MeO

OH

OMe

OMe

OMe

GluO O

OOH

OH

OH

149

151 152
150

147 148

O

O

OH

OH

OH

OH

154

O

O

OH

OH

OH

OH

OH

155

OH

OMe O

OH

OH

153
 

Ormocarpum kirkii also gave four biflavonoids 156-159 (Figure 17) that showed antiplasmodial 

activity toward P. falciparum strain K1; isochamaejasmin (159) was the most active, with an IC50 of 

7.3 μM, but its selectivity was rather limited [60]. 

 

Figure 17. Structures of biflavonoids 156-159. 

 

O

O

OH

OH

O

O OH

OH

H

H
H

H

OH

O

O

OH

OH

O

O

OH

H

H
H

H

OH

O

O

OH

OH

O

O OH

OH

H

H
H

H

OH

OH

157 158

O

O

OH

OH

O

O OH

OH

H

H
H

H

OH

OH

159

156

 



Molecules 2011, 16                            

 

 

2161

4. Alkaloids 

Cassiarin A (160) (Figure 18) from the leaves of Cassia siamea (Leguminosae) showed promising 

antimalarial activities. Cassiarin A had inhibitory effects against P. falciparum (IC50 = 0.02 M). 

Antimalarial activity was assessed in vivo using the 4-day suppressive test procedure. The ED50 value 

of cassiarin A was 0.17 [61]. In contrast, cassiarins C-E (161-163) exhibited moderate antiplasmodial 

activity (IC50 values of 24.2 to 2.3 µM) and no cytotoxicity (IC50  100 µM) [62]. 

Acridone alkaloids have been isolated from the fruits of Zanthoxylum leprieurii (Rutaceae), and 

among them arborinine (164) and xanthoxoline (165) (Figure 18) exhibited a good in vitro 

antiplasmodial activity against the P. falciparum strain 3D7, with IC50 values of 15.8 and 17.0 μM, 

respectively [63]. 

Figure 18. Structures of alkaloids 160-165. 

 

N

OH

O

160

O

N

OH O

N

OHO

O

O

OH

161 162
 

 

 R R1 

164 Me OMe 

165 H OMe 

N

R

O

OMe

OH

R
1

O

N

OHO

N

OH

163

 
 

Flinderole A (166) and isoborreverine (167) have been isolated from Flindersia acuminata 

(Rutaceae) and dimethylisoborreverine (168), flinderoles B (169), and C (170) (Figure 19) have been 

isolated from Flindersia ambionensis. These indole alkaloids were found to have selective 

antiplasmodial activities, with IC50 values of 0.08 to 1.42 μM against the P. falciparum strain Dd2 and 

with selectivity assessed using the mammalian cell line HEK-293 [64]. In addition, the antiplasmodial 

activities of alkaloids 166-170 and voacamine (171) were evaluated using P. falciparum strains with 

different drug-resistance profiles (3D7, FCR3, HB3, and K1). Some differences in the IC50 values 

between the strains were observed. Among these alkaloids, including lirodenine (172) and xylopine 

(173), the dimethylisoborreverine (168) was the most active, with IC50 values between 0.02 μM and 

0.81 μM [65]. 

Violacein (174) is a violet pigment extracted from the gram-negative bacterium Chromobacterium 

violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. In 

addition, at micromolar concentrations it efficiently killed chloroquine-sensitive (3D7) and -resistant 



Molecules 2011, 16                            

 

 

2162

(S20) P. falciparum strains in vitro, inhibited parasitemia in vivo, even after parasite-establishment; 

and protected P. chabaudi chabaudi-infected mice from a lethal challenge [66].  

Figure 19. Structures of alkaloids 166-185. 

 

N
H N N

N

N
H N

H

N

R

H

H

N R

N
H N N

R

N R

 R

166 H

169 CH3

 R

167 H

168 CH3

170

N
H

N

MeO

N
H

N

OMeO

O

MeO

N

O

O

O

NH

O

O

OMe

172 173171 174

N

OMe

O

O

O

OH N

OMe

O

O

MeO

OH

OH

O

O N
+

OH
CF3CO2

-

MeO

MeO N
+

MeO

H

H

OH
H

O

O

O

O

N

O

175 176 177

MeO

OH

O

O

N

H

178

N
H

OHC

OH R

 R

179 H

180 OMe

N

OMe

R

R
1 O

 R R1

181 OMe OMe

182   OCH2O

183 184

N

O

OH
OMe

185

N
H

NH

O NH

O

OH

CF3CO2
-

 
 

A benzylisoquinoline alkaloid 175 and an aporphine alkaloid 176 (Figure 19) isolated from 

Doryphora sassafras (Monimiaceae), when tested against these same P. falciparum strains, exhibited 

IC50 values of 3.0 and 4.4 μM, respectively. Compound 175 was tested for cytotoxicity toward a 



Molecules 2011, 16                            

 

 

2163

human embryonic kidney cell line (HEK293) and showed no activity at 120 μM [67]. The alkaloidal 

components of the Bhutanese medicinal plant Corydalis calliantha (Fumariaceae), which is used for 

the treatment of malaria, have been assessed. Among them, protopine (177) and the cheilanthifoline 

(178) showed promising in vitro antiplasmodial activities against P. falciparum, both wild type (TM4) 

and multidrug-resistant (K1) strains, with IC50 values of 2.78 to 4.29 µM [68]. Alkaloids 179 and 180 

have been isolated from Clausena harmandiana (Rutaceae) and they showed antiplasmodial activity 

with IC50 values of 15.5 and 12.2 µM, respectively, against the P. falciparum strain K1 [69]. 

Furoquinoline alkaloids (181-184) have been obtained from Teclea afzelii (Rutaceae). When evaluated 

against P. falciparum (NF54) in vitro, 3 µM of compounds 181-184 showed a partial suppression of 

parasitic growth [70]. The azafluorenone 5-hydroxy-6-methoxyonychine (185) obtained from 

Mitrephora diversifolia (Annonaceae) was shown to be active against P. falciparum strains 3D7 and 

Dd2, with IC50 values of 9.9 and 11.4 μM, respectively [71]. 

 
Figure 20. Structures of guanidine alkaloids 186-194. 

 

N
+

N N
H

H
O

O

NHN

NH

O O
NHNH2

NH

7

6

X-
X-

N
+

N N
H

H
O

O
NHNH2

NH
8

N

N N
HO

HH

O

O

O

N

O

NH2

NH2

15

N

N N
H

H
O

O

NHN

NH

O O
NHNH2

NH

H

9

n

 n

186 6

187 7

N

N N
H

HHO

ON

N

N
H

H H

n

7

 n

188 7

189 8

N
+

N
H

N
H

H
O

O

NHN

NH

O O
NHNH2

NH

H

9

8

X-

190 191

192 193

X-

N
+

N N
H

H
HO2C

6

194
 



Molecules 2011, 16                            

 

 

2164

Nine guanidine alkaloids 186-194 (Figure 20) from Caribbean marine sponges, including 

Monanchora arbuscula and Clathria calla, were evaluated to determine their activities against human 

cancer cell lines and malaria protozoa; they exhibited IC50 values of 0.1 to 4.5 μM using the  

P. flaciparum strain FcB1 [72]. Zamamidines 195-198 and manzamine A (199) (Figure 21) have been 

isolated from the marine sponge species Amphimedon and have been shown to exhibit inhibitory 

activities against T. brucei (IC50: 1.4, 1.4, 0.4, 7.9, and 0.1 µM, respectively), and P. falciparum (IC50: 

9.6, 16.3, 0.8, 12.4, and 1.8 µM, respectively) in vitro [73].  

 

Figure 21. Structures of alkaloids 195-202. 

 

N

NH

NN
H H

N

NH

H

OH
N

NH

N
+

N
H

O
-

H

OH
N

NH

NN
H H

OH

197 198

N

NH

NN
H H

N

NH

H

OH

195

N

NH

NN
H H

N

NH

H

OH

196

199

N

NH

NN
H H

OH

HCl

N

NH

NN
H H

OH

OH

N

NH

NN
H H

OH

OH
HCl

202201200
 

Acanthostrongylophora ingens has yielded (+)-8-hydroxymanzamine A (200), (+)-manzamine A 

(199), (+)-8-hydroxymanzamine A hydrochloride (201), and (+)-manzamine A hydrochloride (202). 

Compounds 200 and 201 showed equally potent in vitro antiplasmodial activity against chloroquine-

sensitive (D6) and -resistant (W2) strains of P. falciparum (IC50 = 34.6 and 36.6 nM vs. 47.8 and  



Molecules 2011, 16                            

 

 

2165

60.7 nM, respectively), while 199 was >3-fold less potent than 202 (IC50 = 37.9 and 47.1 nM vs. 10.5 

and 12.5 nM, respectively) [74].  

Atisinium chloride (203) (Figure 22) is the major alkaloid from Aconitum orochryseum 

(Ranunculaceae). It was tested for in vitro antiplasmodial activity against the malarial P. falciparum 

strains TM4/8.2 (wild type) and K1CB1 (chloroquine- and antifolate-resistant), and was shown to have 

good antiplasmodial activities, with IC50 values of 4.0 and 3.6 µM, respectively, against the TM4 strain 

and the K1 strain of P. falciparum [75]. 

Glycoalkaloids have been isolated from Solanaceae species, and five of them, chaconine (204), 

solanine (205), solamargine (206), solasonine (207), and tomatine (208) (Figure 22), were evaluated 

against P. yoelii 17XL in mice at different concentrations with a 4-day parasitemia suppression test. 

Chaconine (204) showed a dose-dependent suppression of malaria infection, with an ED50 of  

4.49 mg/kg; therapeutic index (TI) 9. At a dose of 7.50 mg/kg, the percent parasitemia suppression 

values of chaconine, tomatine, solamargine, solasonine, and solanine were 71.38, 65.25, 64.89, 57.47, 

and 41.30%, respectively. At 3.75 mg/kg, the percent parasitemia suppression of chaconine was 

42.66% [76].  

 

Figure 22. Structures of alkaloids 203-208. 

 

O

O

O
O

OH

OH
OH

N

O

O
OH

OH

OH
OH OH

H

H H
H

H
H

O

OOH
OH OH O

O

O
O

OH

OH
OH

N

OH

OH

H

H H
H

H
H

204 205

O

O

O
O

OHOH

O
O

OH

OH
OH

OH OH
OH
OH

NH

H H
H

H
H

O

NH

H H
H

H
H

O

OOH
OH OH O

O

O
OH

OH
OH

OH

OH

OH

206 207

OH
OH

O

OH

OH

OOH
OH

OH

O
O

OH

NH

H H
H

H
H

O
O

O
OH

OH

O

OH

OH

208

OH
N

+

OH

Cl-

203
 



Molecules 2011, 16                            

 

 

2166

The pyridinone alkaloid 209 (Figure 23) has been isolated from an EtOAc extract of a culture 

medium of the fungus Septoria pistaciarum. It exhibited excellent in vitro antiplasmodial activity 

against chloroquine-sensitive (D6) and -resistant (W2) strains of P. falciparum (IC50 values of 0.9 and 

0.5 µM, respectively) and cytotoxic activity toward Vero cells [77].  

Pyrroloiminoquinone alkaloids, discorhabdins A (210) and C (211), and dihydrodiscorhabdin C 

(212) (Figure 23), have been isolated from a deep-water Alaskan sponge species of the genus 

Latrunculia (Latrunculiidae). These alkaloids exhibited anti-HCV activity, antiplasmodial activity 

against P. falciparum strains D6 and W2 (IC50 values of 53, 2800, and 170 nM vs. 53, 2000, and 130 

nM, respectively), and selective antimicrobial activity. Although compounds 210 and 212 displayed 

potent and selective in vitro antiprotozoal activity, P. berghei-infected mice did not respond to these 

metabolites due to their toxicity in vivo [78]. 

 

Figure 23. Structures of alkaloids 209-212. 

 

N
H

N

N
H

O

O

Br

S

N
H

N

N
H

O

O

BrBr

N
H

N

N
H

OH

O

BrBr

210 211 212

N

OH

O

OH

O

H
H

209
 

The bromotyrosine alkaloids psammaplysin G (213) and psammaplysin F (214) (Figure 24) have 

been isolated from the marine sponge Hyattella sp. (Spongiidae). When tested against two different 

strains of the parasite P. falciparum (Dd2 and 3D7), 214 displayed IC50 values of 1.4 and 0.87 μM, 

respectively, while 213 showed 98% inhibition at 40 μM against a chloroquine-resistant (Dd2) strain 

of P. falciparum [79].  

Figure 24. Structures of alkaloids 213-216. 
 

O

Br

Br

MeO
O

N

OH
O

NH O

Br Br

N
R

 R

213 CONH2

214 H

N
H

O
OH

O OH

R

 R

215 Cl

216 H
 

 

Fermentation culture from the endophytic fungus Pestalotiopsis sp. yielded pestalactams A (215) 

and B (216) (Figure 24), which were tested against two different strains of the malaria parasite P. 



Molecules 2011, 16                            

 

 

2167

falciparum (3D7 and Dd2) and parasite growth inhibition of ~16-41% was achieved at 25 µM. 

Citotoxicity toward mammalian cell lines (MCF-7 and NFF) was also evaluated, and modest in vitro 

activity in all assays was observed [80]. 

The β-carboline (+)-7-bromotrypargine (217) (Figure 25) has been isolated from the marine sponge 

Ancorina sp. (Ancorinidae). This alkaloid was tested against both a chloroquine-resistant (Dd2) and 

chloroquine-sensitive (3D7) P. falciparum strains. Preliminary toxicity toward human cells was 

investigated using a human embryonic kidney cell line (HEK293), and 217 had IC50 values of 5.4 μM 

(Dd2) and 3.5 μM (3D7), and was not cytotoxic toward the HEK293 cell line at up to 80 μM [81]. 
 

Figure 25. Structures of β-carboline and bromopyrrole alkaloids 217-232. 

 

217

N
H

Br NH

NH

NH2NH

 R

220 H

221 OH

N
H

Br

O

N

N
N

NH2

O

H
H

R

N
H

Br

R

O

NH

NH
N

NH2

           R

218     H

219     Br

+

N
H

Br

Br

O

NH

N
N

NH2

H
H

TFA-

222

N
H

NH
Br

O

NHN

NH2

Br

N
H

NH

O

Br

NH
N

NH2

O

N
H

NH
Br

O

O

223 224 225

N
Br

NH

Br

O

CO2H

N
Br

NH

Br

O

OH

NH
N

NH2

NH
N

NH2

N
N
H O

H

Br

N
N
H O

H

Br

NH
N

NH2

OH

Cl
NH2

N

N

ON

N

HH

NH2

H

Br Br

H

226 227 228 229
 

N
H

Br

O

N

CO2H

H
N NH

NH2

H

N
H

Br

O

O

NH N

CO2H N
H

Br

O

O
N

+ CO2
-

230 231 232
 

 

Bromopyrrole alkaloids 218, 220, 223, 224, 226, 228, 229, and 232 (Figure 25) obtained from marine 

sponges in the genera Axinella (Axinellidae) and Agelas (Agelasidae) have been screened in vitro against 

four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania 



Molecules 2011, 16                            

 

 

2168

donovani and P. falciparum (strain K1). Longamide B (226) and dibromopalau’amine (229) have been 

shown to be promising trypanocidal and antileishmanial agents, while dispacamide B (220) and 

spongiacidin B (224) showed the highest antiplasmodial activity (IC50 values of 3.3 and 3.4 µM, 

respectively). In addition, an evaluation of the activity of the alkaloids (218-232) tested against three 

different enzymes (PfFabI, PfFabG, PfFabZ), that are involved in de novo fatty acid biosynthesis in  

P. falciparum (PfFAS-II), identified bromopyrrolohomoarginin (230) as a potent inhibitor of PfFabZ. Tests 

against the mammalian L6 cells revealed important clues regarding the therapeutic index of the metabolites 

[82]. 

5. Peptides and Macrocyclic Compounds  

 

Gallinamide A (233) (Figure 26) from the cyanobacteria Schizothrix sp. (Schizotrichaceae) showed 

a reasonably effective antimalarial potency against the P. falciparum strain W2 (IC50 8.4 μM) and 

cytotoxicity toward mammalian Vero cells (IC50 10.4 μM). However, it did not show in vitro 

cytotoxicity toward NCI-H460 human lung tumor or neuro-2a mouse neuroblastoma cell lines at the 

highest concentration tested (16.9 μM) [83]. 

The macrocycles 234 and 235 (Figure 26) are histone deacetylase inhibitors (HDACi) that cause a 

diverse range of responses in biological systems [84]. The antiparasitic capabilities of these 

macrocyclic HDACi were determined against malarial and leishmanial pathogens. Antiparasitic 

activities of macrocyclic HDACi derived from macrolide skeletons are dependent on the length (n) of 

the spacer group that separates their zinc-binding and surface-recognition moieties. Antimalarial 

activities peak when n=6 (IC50 234: 95 nM), whereas antileishmanial activities are optimum when 

n=8–9 (IC50 235: ~3.3 µM). This observation could facilitate the identification of other HDACi that are 

more selective for either parasite [84]. 

 

Figure 26. Structures of peptide and macrocyclic compounds 233-235. 
 

O

N

O

N

OH
OH

O OO

OH

OMe

O

N N

NOHOH

O

N
OH

H
n

 n

234 6

235 9

N
O

O

NH
NH

O

O

O

N

O

O

233

 

6. Phenylalkanoids 

 

6.1. Phenylpropanoids 

The lignan butyrolactone 236 (Figure 27) from the fungus Aspergillus terreus BCC 4651 showed 

antiplasmodial activity against the P. falciparum strain K1 with an IC50 value of 18 µM [85]. The main 

constituent (39.0%) of the volatile constituents of Daucus crinitus was isochavicol isobutyrate (237). 



Molecules 2011, 16                            

 

 

2169

This compound, together with isochavicol (238) and isochavicol propionate (239), exhibited 

antiplasmodial activity against P. falciparum (strain FcB1) with IC50 values of 68.7, 14.2 and 70.0 µM, 

respectively [86]. In contrast, coumarin 240 did not exhibit any significant antiplasmodial activity 

(IC50 value of 146.9 µM against strain D10) [38]. 

 

Figure 27. Structures of phenylpropanoids 236-240. 
 

O

O
OH

OH
O OMe

O

OH

236

OHO

O

238237

O

O

O O

MeO

OH

239 240
 

6.2. Phenylethanoids  

Jacaranda glabra (Bignoniaceae) yielded phenylethanoid glucosides (241-244) and jacaranone 

(245) (Figure 28), which were found to be active in vitro against the P. falciparum strain K1 (IC50 241: 

1.5; 242: 1.0; 243: 0.8; 244: 0.8 and 245: 7.3 μM). All of the compounds except for 241 showed low 

cytotoxicity toward L-6 cells [87]. 

 

Figure 28. Structures of phenylethanoids 241-245. 
 

O
OOH

OH
O

O

O

O OH
O

O
OH

O

242

O
OOH

O
O

O

O

O OH
O

O
OH

O
O

R
1

R

 R R1

241 H H

243 H OH

244 OH H

OH

O
MeO

O

245
 

 

6.3. Phenylmethanoids, benzylesters, and phenolics 

 

A phenol 246 and two phenolic glycosides 247 and 248 (Figure 29) have been isolated from 

Flacourtia indica (Flacourtiaceae), and they have been shown to have antiplasmodial activity toward 

the W2 strain of P. falciparum (IC50 values of 0.7 to 27 µM) [88]. Norbergenin derivatives 249-251 

(Figure 29) isolated from the stem bark of Diospyros sanza-minika (Ebenaceae) were evaluated for 

their in vitro activity against the P. falciparum K1 and cytotoxicity toward MRC-5 cells (249: IC50  



Molecules 2011, 16                            

 

 

2170

8.4 μM; CC50  137.4 μM, 251: IC50 11.3 μM; CC50  147.5 μM, 250: IC50 1.3 μM; CC50 51.5 μM). 

Compound 251 possesses an O-p-hydroxybenzoyl group at C-11, while 249 and 250 have O-galloyl, 

and O-(3′-methylgalloyl) groups, respectively, at C-4, which may play an important role in their 

antimalarial activity [89]. 
 

Figure 29. Structures of phenylmethanoids and phenolics 246-251. 
 

O

O

O

OH

OH OH

H

H
OH

OH

O
O

OH 251

 R

249 OH

250 OMe

O

O

O

OH

OH OH

H

H
OH

O

OH

O

OH OH

R

246

OH

OH
O

O
O

OH
OH

OH

O

OH

O O

O
O

O

OH
OH

OH

O

OH

OH
247

248

 
 

7. 4-Aryl-3,4-dihydrocoumarins 

 

In addition to antiplasmodial biflavonoids, Ormocarpum kirkii (Papilionaceae) yielded  

4-aryl-3,4-dihydrocoumarins 252 and 253, which were active against the P. falciparum strain K1 (IC50 

values of 39.5 and 21.1 μM, respectively) (Figure 30) [90]. 

 

Figure 30. Structures of 4-aryl-3,4-dihydrocoumarin dimers 252 and 253. 
 

O

OO

O

OH

OH

R

OH

R

OH

H

H

H

H

 R 

252 OH 

253 OMe 

 
 



Molecules 2011, 16                            

 

 

2171

8. Xanthones, Naphthopyrones, and Analogues Vismiones 

 

The xanthone 1,5-dihydroxy-3,6-dimethoxy-2,7-diprenylxanthone (254) (Figure 31) showed 

selective activity against P. falciparum with an IC50 value of 7.25 µM. When screened for activity 

against T. cruzi, T. brucei, L. infantum (Ghana strain), S. aureus, and E. coli, and for cytotoxicity 

against MRC-5 cells, it showed IC50 values >64 µM [50]. Xanthones 255-258 and their analogues 259-

261 have been isolated from Cratoxylum maingayi and Cratoxylum cochinchinense (Clusiaceae) [91]. 

These compounds showed antiplasmodial activity against P. falciparum at concentrations of  

11.0 to 1.9 µM. Most of these compounds also showed cytotoxicity toward the NC1-H187 cancer cell 

line [91]. 

Aschernaphthopyrone A (262) has been isolated from the scale insect pathogenic fungus 

Aschersonia paraphysata, and its antiplasmodial activity against the P. falciparum strain K1 (IC50 = 

7.3 μM) is higher than that of hopene triterpene 143 (Figure 15) isolated from the same fungus [51]. 

 

Figure 31. Structures of xanthones, naphthopyrones, and analogues vismiones 254-262. 

 

O

O OH

OMe

OH

MeO
OOH

OH

O OH

OH OOH

OH

O OH

O

254 255 256

OOH

OH

O OH

OO

O OH

OH

OH

257 258

OHO

OH

OH

OMe

259

OO

OH

OH

OMe

OHO

OH

OH

OMe O

O

O

O

OH OH

OH

OH

OH OH

262260 261
 

 
9. Anthraquinones and Anthrones 

 

Demethylmacrosporine (263) (Figure 32) isolated from Rumex obtusifolius (Polygonaceae) showed 

significant activity in the FBIT (Ferriprotoporphyrine biocrystallization inhibition test, IC50 = 0.3 μM) 



Molecules 2011, 16                            

 

 

2172

[21]. The anthrone–anthraquinones scutianthraquinones A, B, and C (264–266), and the  

bisanthrone–anthraquinone scutianthraquinone D (267) have been isolated from the bark of Scutia 

myrtina (Rhamnaceae). Compounds 264-267 and 268 (aloesaponarin I, which was isolated from Aloe 

saponaria - Asphodelaceae) exhibited good antiplasmodial activities against the P. falciparum Dd2 

(IC50 values of 1.1 to 5.6 μM), while compounds 264, 265, and 267 also exhibited good antiplasmodial 

activity against the P. falciparum strain FCM29 (IC50 values of 1.2 to 5.6 μM), these compounds also 

showed weak antiproliferative activity against the ovarian cancer cell line A2780 [92]. 

 

Figure 32. Structures of anthraquinones and anthrones 263-268.  
 

OOH Me

OH

OMe

O

O OH

O

O
Me

OH

OMe

O

O

OOH Me

OH

OMe

O

O OH

O

O
Me

OH

OMe

O

O

264 265

OH

O

O

OH

OH

263

OOH Me

OH

OMe

O

OH
OH

O

O
Me

OH

OMe

O

266

OOH Me

OH

OMe

O

O
OH

O

O
Me

OH

OMe

O
O

O

OMe

OOH

Me

OH

O

O

OH O Me

OH

O

OMe

O

267

268

 
 

10. Halenaquinone Derivatives  

 

Compounds 269-271 (Figure 33) were the most active of a series of halenaquinone derivatives from 

South Pacific marine sponges of the genus Xestospongia (Petrosiidae). The exhibited antiplasmodial 

activity did not depend on the chloroquine-sensitivity of the strain tested, since there was no significant 

difference between the IC50 values for strains FcB1 (IC50 1.1, 3. 9, and 9.2 μM, respectively) and 3D7 

(IC50 1. 7, 4.1, and 10.9 μM, respectively). The three active compounds were also active in protein 

farnesyltransferase bioassays, which may provide insight into their mode of action against  

P. falciparum [22]. 



Molecules 2011, 16                            

 

 

2173

Figure 33. Structures of halenaquinone derivatives and analogues 269-271. 
 

O

O

O

O

O

N
H

S

O O

O

O

O

O

O

S

N
H

OO

269 270

O

O

O

OH

271
 

 

11. Endoperoxides, Peroxides and Other Polyketides from Sponges 

 

Endoperoxyketal polyketides manadoperoxides A-D (272-275) (Figure 34) have been isolated from 

the Indonesian sponge Plakortis cfr. Simplex (Plakinidae), and were assayed in vitro against the D10 

and W2 strains of P. falciparum, where they showed good antimalarial activity (IC50 values of 4.5 to 

10.4 and 2.3 to 7.9 µM, respectively) compared to those of plakortin (276, IC50 value of 0.9 and  

0.4 µM, respectively) and peroxyplakoric B3 ester (277, P. falciparum strain FCR3, IC50 = 1.1 µM), 

the latter of which differs from manadoperoxide B (P. falciparum strain FCR3, IC50 = 6.8 µM) by only 

minor structural details. This difference in the antiplasmodial activity has been explained on the basis 

of a model for the interaction of 1,2-dioxanes with heme and the production of C-centered radicals that 

are toxic to the parasite. For the manadoperoxides, either the endoperoxide linkage is inaccessible to 

the heme iron or the O1 radical cannot evolve to produce a C-centered radical [93]. Another 

polyketide-peroxy, plakortide F (methyl ester 278), has been isolated from a species of Plakortis 

(Plakinidae) from Jamaica. It exhibited good in vitro antiplasmodial activity (IC50 values of 3.4 and  

2.5 µM against P. falciparum D6 and W2 strains, respectively), whereas a non peroxide-polyketide, 

plakortone D (279) (Figure 35), exhibited IC50 values of 7.8 and 8.7 µM, respectively [94].  

Five-membered-ring polyketide endoperoxides 280 and 281, and a cyclic peroxide 282 (Figure 34) 

have been isolated from the sponge Plakortis halichondrioides (Plakinidae). Biological screening of 

these cycloperoxides for cytotoxic activity against various human tumor cell lines revealed that 

compounds 281 and 282 are very active. In assays for antiplasmodial activity, compounds 280-282 

also showed good activity against the pathogenic microbe P. falciparum (IC50 values of 4.0, 0.3 and 

3.0 µM, respectively). Compound 280 also showed antitubercular activity against Mycobacterium 

tuberculosis (IC50 values of 62 and 71 µM, respectively) [95]. 

Gracilioethers A-C (283-285) (Figures 34 and 35) have been isolated from the marine sponge, 

Agelas gracilis (Agelasidae), and they showed antimalarial activity against the ItG strain of  

P. falciparum with IC50 values of 1.6 to 31 μM, and gracilioether B (284) also showed antileishmanial 

activity [96]. Malyngolide dimer (286) (Figure 35) has been isolated from the marine cyanobacterium 

Lyngbya majuscule (Oscillatoriaceae). It exhibited moderate in vitro antiplasmodial activity against 

chloroquine-resistant P. falciparum (W2, IC50 = 19 μM), but roughly equivalent toxicity toward H-460 

human lung cell lines [97]. 

 

 
 



Molecules 2011, 16                            

 

 

2174

Figure 34. Structures of peroxide polyketides 272-278 and 280-282. 

 

274
O

O

OMe

CO 2MeO
O

O

OMe

CO 2Me

R

             R

272      CH3

273      CH2CH3

 

O
O CO 2Me

O
O

OMe

CO 2Me

O
O

OMe

CO 2MeOH

OH

O

O
O

O
O

OH
H H

O O
R

CO 2Me

             R

280      CH3

282       H

278

276

277

275

283

OO

CO 2Me

HO 2C

O O

CO 2H

281

 
 

Figure 35. Structures of other polyketides 279 and 284-286 from sponges. 

 
 

O

O

H

O
O

OO
O

O

OO
O H

284279

286

O

O

O

OH

O H

O

285

 
12. Acetylenes 

 

Three acetylenic compounds, 1-phenyl-hepta-1,3,5-triyne (287), (R)-1,2-dihydroxytrideca-3,5,7,9,11-

pentayne (288), and its glycoside, 2-β-D-glycopyrasyloxy-1-hydroxytrideca-3,5,7,9,11-pentayne (289) 

(Figure 36) have been isolated from Bidens pilosa (Compositae). Among other activities, these 

compounds showed potential antimalarial activity in vitro (determined spectrophotometrically by 

measuring the activity of the pLDH, in control and drug-treated cultures or using the Nagel method 



Molecules 2011, 16                            

 

 

2175

against the RCR-3 strain of P. falciparum) [98, 99]. Compound 287 when tested in vitro showed an 

IC50 = 37.2 µM (P. falciparum strain NF54), while compound 288 showed an IC50 = 1.8 µM. In in vivo 

assays the average 32.8% malaria parasite growth (P. berhei strain NK-65) diminished to 12.1% by 

administration of a dose 0.8 mg/kg of 288 for four days in mice [98, 99]. 

The roots of Tagetes erecta (Compositae) yielded 2-hydroxymethyl-non-3-ynoic acid  

2-[2,2']-bithiophenyl-5-ethyl ester (290). This compound was evaluated for its in vitro antiplasmodial 

activity using the schizont maturation inhibition assay, and showed significant schizonticidal activity 

against both chloroquine-sensitive (MRC-pf-2) and -resistant (MRC-pf-56) strains of P. falciparum 

with IC50 values of 26 and 53 nM, respectively [100].  

 

Figure 36. Structures of polyacetylenes 287-290. 
 

H OR

OH

             R

288       H

289       Glc 

287

290

S S O

O

OH

 
 

-Resorcylic Acid Lactones 

 

The -resorcylic acid lactones paecilomycins (291-294), aigialomycin B (295), aigialomycin D 

(296), and aigialomycin F (297) (Figure 37) were isolated from the mycelial solid culture of 

Paecilomyces sp. (Trichocomaceae, fungus). These lactones exhibited antiplasmodial activity against 

the 3D7 line of P. falciparum, and 294 and 297 were the most active, with IC50 values of 20.0 and 10.9 

nM, respectively, whereas compounds 293-295 showed good activity against the P. falciparum strain 

Dd2, with IC50 values of 1.7 to 13.5 µM [101]. 
 

Figure 37. Structures of -resorcylic acid lactones 291-297. 

 
 

MeO

O

O

O
OH

OH

OH

OH MeO

O

OOH

O
OH

OHOH

MeO

O

O

OH

OH

OH

OH

291 292 293
 

 

 

 

 

 



Molecules 2011, 16                            

 

 

2176

Figure 37. Cont. 

 

MeO

O

O

O
OH

OH

OH

OH

MeO

O

O

OH

OH

OH

OH

OH

O

O

OH

OH

OH

OH

MeO

O

O

OH

OH

OH

OH OH

295294 296

297  
14. Depsidones 

 

The depsidones mollicellins B (298), C (299), E (300), K-M (301-303), and J (304) (Figure 38) 

isolated from Chaetomium brasiliense (Chaetomiaceae) exhibited in vitro antimalarial activity against 

P. falciparum (K1 multidrug-resistant, IC50 = 12.3, 22.0, 7.2, 7.0, 3.1, 8.6, and 12.2 µM, respectively). 

These compounds also showed in vitro cytotoxicity against KB, BC1, and NCI-H187 cells, as well as 

five cholangiocarcinoma cell lines [102]. 

 

Figure 38. Structures of depsidones 298-304.  
 

O

O

O

OH

CHO

OH

OMe

O

R
O

O

O

OH

CHO
R

2

R
R

1

 R R1 R2

302 H =O OH

303 H =O OMe

304 Cl H OH

O

O

O

OH

CHO
O

O
R

 R

298 H

301 Cl

 R

299 H

300 Cl

 
 

15. Benzophenones  

A series of antiplasmodial benzophenones 305-318 (Figure 39), with IC50 values of 3.3 to  

37.2 μM, were isolated from Moronobea coccinea (Clusiaceae). The benzophenone cytotoxicities were 

also evaluated toward the human cell line MRC-5 [103]. Isoxanthochymol (330) from Garcinia spp. 

(Clusiaceae) exhibited broad but non-selective antiprotozoal activity, with an IC50 value of 4.47 µM 

against P. falciparum, and was also cytotoxic (IC50 7.46 µM) [50]. Symphonia globulifera (Clusiaceae) 

also contains polycyclic polyprenylated acylphloroglucinol compounds 317-327 and two oxidized 

derivatives 328 and 329 (Figure 39). All compounds showed antiplasmodial activity when evaluated in 

vitro against a chloroquine-resistant strain of P. falciparum (FcB1), with IC50 values of 2.1 to  

10.1 µM [104]. 



Molecules 2011, 16                            

 

 

2177

Figure 39. Structures of benzophenones 305-330. 

 

O
O

O

O

OH

OH
O

O
O

O

OH

OH

O

O

O

O

OH

OH

H

O

O

O

O

OH

OH

OH

O

O

O

O

OH

OH

OH

O

O

O

O

OH

OH

R

OH

OH

O

O

O

OH

OH

306305 307

308 309

312

OH

O

O

O
OH

OH

O

O

O
OH

OH

313 314

OH

O

O

O
OH

OH

OH

O

O

O
OH

OH

315 316

OH O

O
OH

O

OH

 R

310 

311 

OH

OH

317
 

 



Molecules 2011, 16                            

 

 

2178

Figure 39. Cont. 

 

O O

O
OH

O

OH

O O

O
OH

O

OH

OH

O O

O
OH

O

OH

OH

320

321 322

O O

O

OH

OH

O

O O

O
OH

O

318 319

O O

O
OH

O

OH

OH

R

O

O
OH

O

OH

O
OH

O

O
OH

O

OH

O
OH

325 326

O O

O

O

OH

OH

O

O

O

OH

OH

OH

328 329

O O

O
OH

O

OH

327

O
O

O

O

OH

OH

H

H

 R

323 

324 

OH

OH

330

 



Molecules 2011, 16                            

 

 

2179

16. Miscellaneous Compounds 

 

16.1. Diterpene-benzoate macrolides and analogues 

 

Several bromophycolides 331-347 (Figure 40) with a diterpene-benzoate macrolide carbon skeleton 

have been obtained from the red alga Callophycus serratus (Solieriaceae), and have been shown to 

exhibit excellent to moderate antiplasmodial activity against the P. falciparum strain 3D7 (IC50 values 

of 0.3 to 56 μM) [105]. 
 

Figure 40. Structures of diterpene-benzoate macrolides and analogues 331-347. 

 
 

OH

O

O

OH

Br

OH

OH

O

O

OH

Br

OH

O

O

OH

Br
Br

OH

O

O

OH

Br
Br

OH

O

O

OH

Br

Br

Br

OOH

O

O

Br
Br

OOH

O

O

Br
Br

OH

O

O

OH

Br

Br

Br

331 332 333

334 335 336

337 338 339

OH

O

O

OH

Br

MeO

OH

O

O

OH

Br

OH

Br

OH

O

O

OH

Br

Br

Br

OH

O

O

OH

Br
Br

340 341 342
 

 

 

 

 



Molecules 2011, 16                            

 

 

2180

Figure 40. Cont. 

 

OH

O

O

H

OH

Br

O
OH

O

O

Br

Br

Br
OH

OH

O

O

Br

OH

Br
OH

343 344 345

OH

O

O

Br

Br

Br
OH

OH

O

O

Br

OH

Br
OH

346 347
 

16.2. Strobilurins 

 

Strobilurins 348-352, two of which (348 and 349) are monochlorinated (Figure 41), have been 

obtained from the fungus Favolaschia tonkinensis. In addition to their antifungal and cytotoxic 

activities, they also exhibited antiplasmodial activity against the P. falciparum strain K1, with IC50 

values of 0.06 to 10.3 µM [106]. 

 

Figure 41. Structures of strobilurins 348-352. 

 
 

MeO

Cl

OMe

MeO2C
OMe

OMe

MeO2C
OMe

OMe

OMe OMe

CO2Me

MeO

Cl

348 349 350

OMe

MeO2C
OMe

O

O

O

OMe

OMe

CO2Me

351 352
 

 
 
 
 
 



Molecules 2011, 16                            

 

 

2181

16.3. Other compounds 

 

Isariotin F (353) (Figure 42) isolated from the fungus Isaria tenuipes also exhibited activity against 

the malaria parasite P. falciparum K1 with an IC50 value of 5.1 μM, as well as cytotoxic activities 

toward cancer cell lines (IC50 values of 15.8, 2.4, and 1.6 μM, in KB, BC, and NCI-H187, respectively) 

and nonmalignant (Vero) cells (IC50 = 2.9 μM) [107]. 

 

Figure 42. Structures of compounds 353-355. 
 

O
OH H

O Cl

NH OH

O

353

OMe

O

OH

BrBr

OH

354

O

O

H

355
 

From the marine sponge Pseudoceratina sp. (Pseudoceratinidae) was isolated a derivative of 

homogentisic acid (354) (Figure 43), which inhibited a specific protein kinase of P. falciparum (Pfnek-1) 

with an IC50 of around 1.8 μM. This product was active in vitro assays against the P. falciparum strain 

FcB1 (IC50 = 12 μM) [108].  

Compound 355 (Figure 42) has been obtained from the fungus Emericella rugulosa. It exhibited 

good antiplasmodial activity against the P. falciparum strain K1 (IC50 value of 5.1 μM), 

antimycobacterial (MIC value of 33.1 μM) activity, and cytotoxicity against three cancer cell lines 

(IC50 value of 3.5, 6.9, and 3.5 μM, in BC1, KB, and NCI-H187, respectively) [109]. 

Chromenes from Cassia siamea (Leguminosae) 356-358 (Figure 43) exhibited good antiplasmodial 

activity against the P. falciparum strain 3D7 (IC50 356: 2.3 μM; 357: 4.7 μM; 358: 8.6 μM) and no 

cytotoxicity (IC50  100 µM) [62]. 

Figure 43. Structures of chromenes 356-358. 

O

O

O

356 357 358

O

O

O O

O

O

OH

 
 

The 6-(8'Z-pentadecenyl)-salicylic acid (359) (Figure 44) isolated from Viola websteri (Violaceae) 

was found to have antimalarial activity in vivo. When tested against P. berghei in mice 6-SA, at 5, 10 

and 25 mg/kg/day exhibited a significant blood schizonticidal activity, and at these concentrations no 

marked toxicity was observed in mice [110]. Another polyketide derivative (malabaricone A, 360) has 

been isolated from Knema glauca (Myristicaceae). It showed moderate cytotoxicity, antituberculosis 



Molecules 2011, 16                            

 

 

2182

activity against M. tuberculosis, and antiplasmodial activity against the parasite P. falciparum strain 

K1 with an IC50 value of 8.6 μM [111]. 

 

Figure 44. Structures of compounds 359 and 360. 
 

OH

OH O

360

CO2H

5

359
 

4. Conclusions  

A few drugs, alone or in combination—chloroquine, primaquine, mefloquine, halofantrine, 

artemisinin, atovaquone, among others—have been used in chemotherapy for malaria. However, the 

evolution of drug- or multidrug-resistance has been a challenge for the effectiveness of such 

chemotherapy. None of the papers in this review claim to have discovered the next antimalarial drug. 

Instead, they provide a remarkable diversity of new natural products on which to base the discovery 

and development of antimalarial drugs. This considerable structural diversity is represented in the 360 

relevant structures that we examined (as illustrated in Figures 1-44). Several potent antiplasmodial 

natural products have been described, and those belonging to alkaloid (manzamine, pyridinone, and 

pyrroloiminoquinone), polyacetylene, phenylethanoid, anthraquinone, polyketide (endoperoxide), 

nonpeptide macrocyclic, and β-resorcylic lactone classes have high antiplasmodial activity. Most of the 

active compounds described here have only been evaluated by in vitro assays, few have been evaluated 

for cytotoxicity, and still fewer have been assayed in vivo. The compounds listed (Figures 1-44) have 

been included based on the potency and/or selectivity of their biological properties, and reflect the 

tremendous effort that is being devoted to recognizing the potential of natural products as lead 

compounds in the treatment of malaria. 

Acknowledgements 

 

The authors thank the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and 

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq/MCT/MS/PRONEX, Brazil, 

Process nos. 555675/2009-2 and 575746/2008-4) for financial support and fellowships.  

References 

 

1. Watts, K.R.; Tenney, K.; Crews, P. The structural diversity and promise of antiparasitic marine 

invertebrate-derived small molecules. Curr. Opin. Biotechnol. 2010, 21, 808-818. 

2. Singh, B.; Sung, L.K.; Matusop, A.; Radhakrishnan, A.; Shamsul, S.S.G.; Cox-Singh, J.; 

Thomas, A.; Conway, D.J. A large focus of naturally acquired Plasmodium knowlesi infections in 

human beings. Lancet 2004, 363, 1017-1024. 



Molecules 2011, 16                            

 

 

2183

3. Vogel, G. Infectious disease - New map illustrates risk from the 'other' malaria. Science 2010, 

329, 618-618. 

4. Fidock, D.A. Drug discovery - Priming the antimalarial pipeline. Nature 2010, 465, 297-298. 

5. Mendis, K.; Rietveld, A.; Warsame, M.; Bosman, A.; Greenwood, B.; Wernsdorfer, W.H. From 

malaria control to eradication: The WHO perspective. Trop. Med. Intern. Health 2009, 14,  

802-809. 

6. Wells, T.N.C.; Alonso, P.L.; Gutteridge, W.E. New medicines to improve control and contribute 

to the eradication of malaria. Nat. Rev. Drug Discov. 2009, 8, 879-891. 

7. Gamo, F.J.; Sanz, L.M.; Vidal, J.; de Cozar, C.; Alvarez, E.; Lavandera, J.L.; Vanderwall, D.E.; 

Green, D.V.S.; Kumar, V.; Hasan, S.; Brown, J.R.; Peishoff, C.E.; Cardon, L.R.; Garcia-Bustos, 

J.F. Thousands of chemical starting points for antimalarial lead identification. Nature 2010, 465, 

305-310. 

8. Camargo, L.M.; de Oliveira, S.; Basano, S.; Garcia, C.R. Antimalarials and the fight against 

malaria in Brazil. Ther. Clin. Risk Manag. 2009, 5, 311-317. 

9. Fattorusso, E.; Taglialatela-Scafati, O. Marine Antimalarials. Mar. Drugs 2009, 7, 130-152. 

10. Bero, J.; Frédérich, M.; Quetin-Leclercq, J. Antimalarial compounds isolated from plants used in 

traditional medicine. J. Pharm. Pharmacol. 2009, 61, 1401-1433. 

11. Magadula, J.J.; Erasto, P. Bioactive natural products derived from the East African flora. Nat. 

Prod. Rep. 2009, 26, 1535-1554. 

12. Batista, R.; Silva, A.D.J.; de Oliveira, A.B. Plant-derived antimalarial agents: new leads and 

efficient phytomedicines. Part II. Non-alkaloidal natural products. Molecules 2009, 14,  

3037-3072. 

13. Sivonen, K.; Leikoski, N.; Fewer, D.P.; Jokela, J. Cyanobactins-ribosomal cyclic peptides 

produced by cyanobacteria. Appl. Microbiol. Biotechnol. 2010, 86, 1213-1225. 

14.  Mariath, I.R.; Falcão, H.D.; Barbosa-Filho, J.M.; de Sousa, L.C.F.; Tomaz, A.C.A.; Batista, L.M.; 

Diniz, M.F.F.M.; Athayde, P.F.; Tavares, J.F.; Silva, M.S.; da Cunha, E.V.L. Plants of the 

American continent with antimalarial activity. Rev. Bras. Farmacogn. 2009, 19, 158-192. 

15 Gademann, K.; Kobylinska, J. Antimalarial natural products of marine and freshwater origin. 

Chem. Rec. 2009, 9, 187-198. 

16 Wright, C.W. Recent developments in research on terrestrial plants used for the treatment of 

malaria. Nat. Prod. Rep. 2010, 27, 961-968. 

17. Krettli, A.U. Antimalarial drug discovery: screening of Brazilian medicinal plants and purified 

compounds. Expert Opin. Drug Discov. 2009, 4, 95-108. 

18. Kaur, K.; Jain, M.; Kaur, T.; Jain, R. Antimalarials from nature. Bioorg. Med. Chem. 2009, 17, 

3229-3256. 

19. Ikegami-Kawai, M.; Arai, C.; Ogawa, Y.; Yanoshita, R.; Ihara, M. Selective accumulation of a 

novel antimalarial rhodacyanine derivative, SSJ-127, in an organelle of Plasmodium berghei. 

Bioorg. Med. Chem. 2010, 18, 7804-7808. 

20. Corbett, Y.; Herrera, L.; Gonzalez, J.; Cubilla, L.; Capson, T.L.; Coley, P.D.; Kursar, T.A.; 

Romero, L.I.; Ortega-Barria, E. A novel DNA-based microfluorimetric method to evaluate 

antimalarial drug activity. Am. J. Trop. Med. Hyg. 2004, 70, 119-124. 



Molecules 2011, 16                            

 

 

2184

21.  Ibáñez-Calero, S.L.; Jullian, V.; Sauvain, M. A new anthraquinone isolated from Rumex 

obtusifolius. Rev. Boliv. Quím. 2009, 26, 49-56. 

22.  Longeon, A.; Copp, B.R.; Roué, M.; Dubois, J.; Valentin, A.; Petek, S.; Debitus, C.;  

Bourguet-Kondracki, M.L. New bioactive halenaquinone derivatives from South Pacific marine 

sponges of the genus Xestospongia. Bioorg. Med. Chem. 2010, 18, 6006-6011. 

23.  Pabón, A.; Deharo, E.; Zuluaga, L.; Maya, J.D.; Saez, J.; Blair, S. Plasmodium falciparum: 

Effect of Solanum nudum steroids on thiol contents and β-hematin formation in parasitized 

erythrocytes. Exp. Parasitol. 2009, 122, 273-279. 

24.  Krettli, A.U.; Adebayo, J.O.; Krettli, L.G. Testing of natural products and synthetic molecules 

aiming at new antimalarials. Current Drug Targets 2009, 10, 261-270. 

25.  Wein, S.; Maynadier, M.; Van Ba, C.T.; Cerdan, R.; Peyrottes, S.; Fraisse, L.; Vial, H. Reliability 

of antimalarial sensitivity tests depends on drug mechanisms of action. J. Clin. Microbiol. 2010, 

48, 1651-1660. 

26.  Tamura, S.; Kubata, B.K.; Syamsurizal; Itagaki, S.; Horii, T.; Taba, M.K.; Murakami, N. New 

anti-malarial phenylpropanoid conjugated iridoids from Morinda morindoides. Bioorg. Med. 

Chem. Lett. 2010, 20, 1520-1523. 

27.  Soni, S.; Gupta, S. In vitro anti-plasmodial activity of Enicostemma littorale. Am. J. Infect. Dis. 

2009, 5, 259-262. 

28.  Afolayan, A.F.; Mann, M.G.A.; Lategan, C.A.; Smith, P.J.; Bolton, J.J.; Beukes, D.R. 

Antiplasmodial halogenated monoterpenes from the marine red alga Plocamium cornutum. 

Phytochemistry 2009, 70, 597-600. 

29.  Isaka, M.; Srisanoh, U.; Veeranondha, S.; Choowong, W.; Lumyong, S. Cytotoxic eremophilane 

sesquiterpenoids from the saprobic fungus Berkleasmium nigroapicale BCC 8220. Tetrahedron 

2009, 65, 8808-8815. 

30.  Pedersen, M.M.; Chukwujekwu, J.C.; Lategan, C.A.; van Staden, J.; Smith, P.J.; Staerk, D. 

Antimalarial sesquiterpene lactones from Distephanus angulifolius. Phytochemistry 2009, 70, 

601-607. 

31.  Efange, S.M.N.; Brun, R.; Wittlin, S.; Connolly, J.D.; Hoye, T.R.; McAkam, T.; Makolo, F.L.; 

Mbah, J.A.; Nelson, D.P.; Nyongbela, K.D.; Wirmum, C.K. Okundoperoxide, a bicyclic 

cyclofarnesylsesquiterpene endoperoxide from Scleria striatinux with antiplasmodial activity. J. 

Nat. Prod. 2009, 72, 280-283. 

32.  Kim, J.J.; Chung, I.M.; Jung, J.C.; Kim, M.Y.; Moon, H.I. In vivo antiplasmodial activity of 

11(13)-dehydroivaxillin from Carpesium ceruum. J. Enzyme Inhib. Med. Chem. 2009, 24,  

247-250.  

33.  Schmidt, T.J.; Nour, A.M.M.; Khalid, S.A.; Kaiser, M.; Brun, R. Quantitative  

structure- antiprotozoal activity relationships of sesquiterpene lactones. Molecules 2009, 14, 

2062-2076. 

34.  Rodríguez, I.I.; Rodríguez, A.D.; Zhao, H. Aberrarone: A gorgonian-derived diterpene from 

Pseudopterogorgia elisabethae. J. Org. Chem. 2009, 74, 7581-7584. 

35.  Wei, X.; Rodríguez, A.D.; Baran, P.; Raptis, R.G. Dolabellane-type diterpenoids with 

antiprotozoan activity from a Southwestern Caribbean gorgonian octocoral of the genus Eunicea. 

J. Nat. Prod. 2010, 73, 925-934. 



Molecules 2011, 16                            

 

 

2185

36.  Sathe, M.; Ghorpade, R.; Srivastava, A.K.; Kaushik, M.P. In vivo antimalarial evaluation of 

gomphostenins. J. Ethnopharmacol. 2010, 130, 171-174. 

37.  Sathe, M.; Kaushik, M.P. Gomphostenins: Two new antimalarial compounds from the leaves of 

Gomphostemma niveum. Bioorg. Med. Chem. Lett. 2010, 20, 1312-1314. 

38.  Mthembu, X.S.; Van Heerden, F.R.; Fouché, G. Antimalarial compounds from Schefflera 

umbellifera. S. Afr. J. Bot. 2010, 76, 82-85. 

39.  Wattanapiromsakul, C.; Chanthathamrongsiri, N.; Bussarawit, S.; Yuenyongsawad, S.; 

Plubrukarn, A.; Suwanborirux, K. 8-Isocyanoamphilecta-11(20), 15-diene, a new antimalarial 

isonitrile diterpene from the sponge Ciocalapata sp. Can. J. Chem. 2009, 87, 612-618. 

40.  Wright, A.D.; Lang-Unnasch, N. Diterpene formamides from the tropical marine sponge 

Cymbastela hooperi and their antimalarial activity in vitro. J. Nat. Prod. 2009, 72, 492-495. 

41.  Herath, H.M.T.B.; Herath, W.H.M.W.; Carvalho, P.; Khan, S.I.; Tekwani, B.L.; Duke, S.O.; 

Tomaso-Peterson, M.; Nanayakkara, N.P.D. Biologically active tetranorditerpenoids from the 

fungus Sclerotinia homoeocarpa causal agent of dollar spot in turfgrass. J. Nat. Prod. 2009, 72, 

2091-2097. 

42.  Dettrakul, S.; Surerum, S.; Rajviroongit, S.; Kittakoop, P. Biomimetic transformation and 

biological activities of globiferin, a terpenoid benzoquinone from Cordia globifera. J. Nat. Prod. 

2009, 72, 861-865. 

43.  Rao, T.S.P.; Sarma, N.S.; Murthy, Y.L.N.; Kantamreddi, V.; Wright, C.W.; Parameswaran, P.S. 

New polyhydroxy sterols from the marine sponge Callyspongia fibrosa (Ridley & Dendly). 

Tetrahedron Lett. 2010, 51, 3583-3586. 

44.  Oshimi, S.; Takasaki, A.; Hirasawa, Y.; Hosoya, T.; Awang, K.; Hadi, A.H.A.; Ekasari, W.; 

Widyawaruyanti, A.; Morita, H. Delaumonones A and B, new antiplasmodial quassinoids from 

Laumoniera bruceadelpha. Chem. Pharm. Bull. 2009, 57, 867-869. 

45.  Houël, E.; Bertani, S.; Bourdy, G.; Deharo, E.; Jullian, V.; Valentin, A.; Chevalley, S.; Stien, D. 

Quassinoid constituents of Quassia amara L. leaf herbal tea. Impact on its antimalarial activity 

and cytotoxicity. J. Ethnopharmacol. 2009, 126, 114-118. 

46.  Cachet, N.; Hoakwie, F.; Bertani, S.; Bourdy, G.; Deharo, E.; Stien, D.; Houel, E.; Gornitzka, H.; 

Fillaux, J.; Chevalley, S.; Valentin, A.; Jullian, V. Antimalarial activity of simalikalactone E, a 

new quassinoid from Quassia amara L. (Simaroubaceae). Antimicrob. Agents Chemother. 2009, 

53, 4393-4398. 

47.  Chianese, G.; Yerbanga, S.R.; Lucantoni, L.; Habluetzel, A.; Basilico, N.; Taramelli, D.; 

Fattorusso, E.; Taglialatela-Scafati, O. Antiplasmodial triterpenoids from the fruits of Neem, 

Azadirachta indica. J. Nat. Prod. 2010, 73, 1448-1452. 

48.  Ramalhete, C.; Lopes, D.; Mulhovo, S.; Molnár, J.; Rosário, V.E.; Ferreira, M.J.U. New 

antimalarials with a triterpenic scaffold from Momordica balsamina. Bioorg. Med. Chem. 2010, 

18, 5254-5260. 

49.  Adams, M.; Christen, M.; Plitzko, I.; Zimmermann, S.; Brun, R.; Kaiser, M.; Hamburger, M. 

Antiplasmodial lanostanes from the Ganoderma lucidum mushroom. J. Nat. Prod. 2010, 73,  

897-900. 



Molecules 2011, 16                            

 

 

2186

50.  Elfita, E.; Muharni, M.; Latief, M.; Darwati, D.; Widiyantoro, A.; Supriyatna, S.; Bahti, H.H.; 

Dachriyanus, D.; Cos, P.; Maes, L.; Foubert, K.; Apers, S.; Pieters, L. Antiplasmodial and other 

constituents from four Indonesian Garcinia spp. Phytochemistry 2009, 70, 907-912. 

51.  Isaka, M.; Yangchum, A.; Rachtawee, P.; Komwijit, S.; Lutthisungneon, A. Hopane-type 

triterpenes and binaphthopyrones from the scale insect pathogenic fungus Aschersonia 

paraphysata BCC 11964. J. Nat. Prod. 2010, 73, 688-692. 

52.  Maregesi, S.M.; Hermans, N.; Dhooghe, L.; Cimanga, K.; Ferreira, D.; Pannecouque, C.; Vanden 

Berghe, D.A.; Cos, P.; Maes, L.; Vlietinck, A.J.; Apers, S.; Pieters, L. Phytochemical and 

biological investigations of Elaeodendron schlechteranum. J. Ethnopharmacol. 2010, 129,  

319-326. 

53.  Sá, M.S. de; Costa, J.F.O.; Krettli, A.U.; Zalis, M.G.; Maia, G.L. de A.; Sette, I.M.F.; Câmara, C. 

de A.; Barbosa-Filho, J.M.; Giulietti-Harley, A.M.; dos Santos, R.R.; Soares, M.B.P. 

Antimalarial activity of betulinic acid and derivatives in vitro against Plasmodium falciparum 

and in vivo in P. berghei-infected mice. Parasitol. Res. 2009, 105, 275-279. 

54.  Santos, D.A.P.; Braga, P.A.C.; Silva, M.F.G.F.; Fernandes, J.B.; Vieira, P.C.; Magalhães, A.F.; 

Magalhães, E.G.; Marsaioli, A.J.; Moraes, V.R.S.; Rattray, L.; Croft, S.L. Anti-African 

trypanocidal and antimalarial activity of natural flavonoids, dibenzoylmethanes and synthetic 

analogues. J. Pharm. Pharmacol. 2009, 61, 257-266. 

55.  Agnihotri, V.K.; ElSohly, H.N.; Smillie, T.J.; Khan, I.A.; Walker, L.A. Constituents of Leonotis 

leonurus flowering tops. Phytochemistry Lett. 2009, 2, 103-105. 

56.  Adams, M.; Plitzko, I.; Kaiser, M.; Brun, R.; Hamburger, M. HPLC-profiling for antiplasmodial 

compounds - 3-Methoxycarpachromene from Pistacia atlantica. Phytochemistry Lett. 2009, 2, 

159-162. 

57.  Songsiang, U.; Wanich, S.; Pitchuanchom, S.; Netsopa, S.; Uanporn, K.; Yenjai, C. Bioactive 

constituents from the stems of Dalbergia parviflora. Fitoterapia 2009, 80, 427-431. 

58.  Froelich, S.; Schubert, C.; Jenett-Siems, K. Antimalarials from prenylated chalcone derivatives 

of hops. In Beer in Health and Disease Prevention; Preedy, V. R., Ed.; Elsevier/Academic Press: 

Amsterdam, Netherlands, 2009; pp. 747-752. 

59.  Cimanga, R.K.; Tona, G.L.; Kambu, O.K.; Mesia, G.K.; Muyembe, J.J.T.; Apers, S.; Totte, J.; 

Pieters, L.; Vlietinck, A.J. Antimalarial, antiamoebic and cytotoxic activities of some extracts 

and isolated constituents from the leaves of Morinda morindoides (Baker) Milne-Redh. 

(Rubiaceae). Recent Prog. Med. Plants 2009, 25, 225-242. 

60.  Dhooghe, L.; Maregesi, S.; Mincheva, I.; Ferreira, D.; Marais, J.P.J.; Lemière, F.; Matheeussen, 

A.; Cos, P.; Maes, L.; Vlietinck, A.; Apers, S.; Pieters, L. Antiplasmodial activity of  

(I-3,II-3)-biflavonoids and other constituents from Ormocarpum kirkii. Phytochemistry 2010, 71, 

785-791. 

61.  Ekasari, W.; Widyawaruyanti, A.; Zaini, N.C.; Syafruddin, D.; Honda, T.; Morita, H. 

Antimalarial activity of Cassiarin a from the leaves of Cassia siamea. Heterocycles 2009, 78, 

1831-1836. 

62.  Oshimi, S.; Deguchi, J.; Hirasawa, Y.; Ekasari, W.; Widyawaruyanti, A.; Wahyuni, T.S.; Zaini, 

N.C.; Shirota, O.; Morita, H. Cassiarins C-E, antiplasmodial alkaloids from the flowers of Cassia 

siamea. J. Nat. Prod. 2009, 72, 1899-1901. 



Molecules 2011, 16                            

 

 

2187

63.  Tchinda, A.T.; Fuendjiep, V.; Sajjad, A.; Matchawe, C.; Wafo, P.; Khan, S.; Tane, P.; 

Choudhary, M.I. Bioactive compounds from the fruits of Zanthoxylum leprieurii. 

Pharmacologyonline 2009, 1, 406-415. 

64.  Fernandez, L.S.; Buchanan, M.S.; Carroll, A.R.; Feng, Y.J.; Quinn, R.J.; Avery, V.M. 

Flinderoles A-C: Antimalarial bis-indole alkaloids from Flindersia species. Org. Lett. 2009, 11, 

329-332. 

65.  Fernandez, L.S.; Sykes, M.L.; Andrews, K.T.; Avery, V.M. Antiparasitic activity of alkaloids 

from plant species of Papua New Guinea and Australia. Int. J. Antimicrob. Agents 2010, 36,  

275-279. 

66.  Lopes, S.C.P.; Blanco, Y.C.; Justo, G.Z.; Nogueira, P.A.; Rodrigues, F.L.S.; Goelnitz, U.; 

Wunderlich, G.; Facchini, G.; Brocchi, M.; Duran, N.; Costa, F.T.M. Violacein extracted from 

Chromobacterium violaceum inhibits Plasmodium growth in vitro and in vivo. Antimicrob. 

Agents Chemother. 2009, 53, 2149-2152. 

67.  Buchanan, M.S.; Davis, R.A.; Duffy, S.; Avery, V.M.; Quinn, R.J. Antimalarial 

benzylisoquinoline alkaloid from the rainforest tree Doryphora sassafras. J. Nat. Prod. 2009, 72, 

1541-1543. 

68.  Wangchuk, P.; Bremner, J.B.; Samten; Rattanajak, R.; Kamchonwongpaisan, S. Antiplasmodial 

agents from the Bhutanese medicinal plant Corydalis calliantha. Phytother. Res. 2010, 24,  

481-485. 

69.  Thongthoom, T.; Songsiang, U.; Phaosiri, C.; Yenjai, C. Biological activity of chemical 

constituents from Clausena harmandiana. Arch. Pharmacal. Res. 2010, 33, 675-680. 

70.  Wansi, J.D.; Hussain, H.; Tcho, A.T.; Kouam, S.F.; Specht, S.; Sarite, S.R.; Hoerauf, A.; Krohn, 

K. Antiplasmodial activities of furoquinoline alkaloids from Teclea afzelii. Phytother. Res. 2010, 

24, 775-777. 

71.  Mueller, D.; Davis, R.A.; Duffy, S.; Avery, V.M.; Camp, D.; Quinn, R.J. Antimalarial activity of 

azafluorenone alkaloids from the Australian tree Mitrephora diversifolia. J. Nat. Prod. 2009, 72, 

1538-1540. 

72.  Laville, R.; Thomas, O.P.; Berrué, F.; Marquez, D.; Vacelet, J.; Amade, P. Bioactive guanidine 

alkaloids from two Caribbean marine sponges. J. Nat. Prod. 2009, 72, 1589-1594. 

73.  Yamada, M.; Takahashi, Y.; Kubota, T.; Fromont, J.; Ishiyama, A.; Otoguro, K.; Yamada, H.; 

Omura, S.; Kobayashi, J. Zamamidine C, 3,4-dihydro-6-hydroxy-10,11-epoxymanzamine A, and 

3,4-dihydromanzamine J N-oxide, new manzamine alkaloids from sponge Amphimedon sp. 

Tetrahedron 2009, 65, 2313-2317. 

74.  Samoylenko, V.; Khan, S.I.; Jacob, M.R.; Tekwani, B.L.; Walker, L.A.; Hufford, C.D.; 

Muhammad, I. Bioactive (+)-manzamine A and (+)-8-hydroxymanzamine A tertiary bases and 

salts from Acanthostrongylophora ingens and their preparations. Nat. Prod. Commun. 2009, 4, 

185-192. 

75.  Wangchuk, P.; Bremner, J.B.; Samten; Skelton, B.W.; White, A.H.; Rattanajak, R.; 

Kamchonwongpaisan, S. Antiplasmodial activity of atisinium chloride from the Bhutanese 

medicinal plant, Aconitum orochryseum. J. Ethnopharmacol. 2010, 130, 559-562. 



Molecules 2011, 16                            

 

 

2188

76.  Chen, Y.; Li, S.Y.; Sun, F.; Han, H.; Zhang, X.; Fan, Y.Y.; Tai, G.H.; Zhou, Y.F. In vivo 

antimalarial activities of glycoalkaloids isolated from Solanaceae plants. Pharm. Biol. 2010, 48, 

1018-1024. 

77.  Kumarihamy, M.; Fronczek, F.R.; Ferreira, D.; Jacob, M.; Khan, S.I.; Nanayakkara, N.P.D. 

Bioactive 1,4-dihydroxy-5-phenyl-2-pyridinone alkaloids from Septoria pistaciarum. J. Nat. 

Prod. 2010, 73, 1250-1253. 

78.  Na, M.; Ding, Y.; Wang, B.; Tekwani, B.L.; Schinazi, R.F.; Franzblau, S.; Kelly, M.; Stone, R.; 

Li, X.-C.; Ferreira, D.; Hamann, M.T. Anti-infective discorhabdins from a deep-water Alaskan 

sponge of the genus Latrunculia. J. Nat. Prod. 2010, 73, 383-387. 

79.  Yang, X.Z.; Davis, R.A.; Buchanan, M.S.; Duffy, S.; Avery, V.M.; Camp, D.; Quinn, R.J. 

Antimalarial bromotyrosine derivatives from the Australian marine sponge Hyattella sp. J. Nat. 

Prod. 2010, 73, 985-987. 

80.  Davis, R.A.; Carroll, A.R.; Andrews, K.T.; Boyle, G.M.; Tran, T.L.; Healy, P.C.; Kalaitzis, J.A.; 

Shivas, R.G. Pestalactams A-C: novel caprolactams from the endophytic fungus Pestalotiopsis 

sp. Org. Biomol. Chem. 2010, 8, 1785-1790. 

81.  Davis, R.A.; Duffy, S.; Avery, V.M.; Camp, D.; Hooper, J.N.A.; Quinn, R.J.  

(+)-7-Bromotrypargine: an antimalarial β-carboline from the Australian marine sponge Ancorina 

sp. Tetrahedron Lett. 2010, 51, 583-585. 

82.  Scala, F.; Fattorusso, E.; Menna, M.; Taglialatela-Scafati, O.; Tierney, M.; Kaiser, M.; Tasdemir, 

D. Bromopyrrole alkaloids as lead compounds against protozoan parasites. Mar. Drugs 2010, 8, 

2162-2174. 

83.  Linington, R.G.; Clark, B.R.; Trimble, E.E.; Almanza, A.; Ureña, L.D.; Kyle, D.E.; Gerwick, 

W.H. Antimalarial peptides from marine cyanobacteria: Isolation and structural elucidation of 

gallinamide A. J. Nat. Prod. 2009, 72, 14-17. 

84.  Guerrant, W.; Mwakwari, S.C.; Chen, P.C.; Khan, S.I.; Tekwani, B.L.; Oyelere, A.K. A  

structure-activity relationship study of the antimalarial and antileishmanial activities of 

nonpeptide macrocyclic histone deacetylase inhibitors. ChemMedChem 2010, 5, 1232-1235. 

85.  Haritakun, R.; Rachtawee, P.; Chanthaket, R.; Boonyuen, N.; Isaka, M. Butyrolactones from the 

fungus Aspergillus terreus BCC 4651. Chem. Pharm. Bull. 2010, 58, 1545-1548. 

86.  Lanfranchi, D.A.; Laouer, H.; El Kolli, M.; Prado, S.; Maulay-Bailly, C.; Baldovini, N. Bioactive 

phenylpropanoids from Daucus crinitus Desf. from Algeria. J. Agric. Food Chem. 2010, 58, 

2174-2179. 

87.  Gachet, M.S.; Kunert, O.; Kaiser, M.; Brun, R.; Muñoz, R.A.; Bauer, R.; Schühly, W.  

Jacaranone-derived glucosidic esters from Jacaranda glabra and their activity against 

Plasmodium falciparum. J. Nat. Prod. 2010, 73, 553-556. 

88.  Kaou, A.M.; Mahiou-Leddet, V.; Canlet, C.; Debrauwer, L.; Hutter, S.; Laget, M.; Faure, R.; 

Azas, N.; Ollivier, E. Antimalarial compounds from the aerial parts of Flacourtia indica 

(Flacourtiaceae). J. Ethnopharmacol. 2010, 130, 272-274. 

89.  Tangmouo, J.G.; Ho, R.; Matheeussen, A.; Lannang, A.M.; Komguem, J.; Messi, B.B.; Maes, L.; 

Hostettmann, K. Antimalarial activity of extract and norbergenin derivatives from the stem bark 

of Diospyros sanza-minika A. Chevalier (Ebenaceae). Phytother. Res. 2010, 24, 1676-1679. 



Molecules 2011, 16                            

 

 

2189

90.  Dhooghe, L.; Maregesi, S.; Maes, L.; Cos, P.; Apers, S.; Vlietinck, A.; Pieters, L. Bioassay 

guided isolation of antiplasmodial constituents from Ormocarpum kirkii. Planta Med. 2009, 75, 

904-904. 

91.  Laphookhieo, S.; Maneerat, W.; Koysomboon, S. Antimalarial and cytotoxic phenolic 

compounds from Cratoxylum maingayi and Cratoxylum cochinchinense. Molecules 2009, 14, 

1389-1395. 

92.  Hou, Y.; Cao, S.; Brodie, P.J.; Callmander, M.W.; Ratovoson, F.; Rakotobe, E.A.; Rasamison, 

V.E.; Ratsimbason, M.; Alumasa, J.N.; Roepe, P.D.; Kingston, D.G.I. Antiproliferative and 

antimalarial anthraquinones of Scutia myrtina from the Madagascar forest. Bioorg. Med. Chem. 

2009, 17, 2871-2876. 

93.  Fattorusso, C.; Persico, M.; Calcinai, B.; Cerrano, C.; Parapini, S.; Taramelli, D.; Novellino, E.; 

Romano, A.; Scala, F.; Fattorusso, E.; Taglialatela-Scafati, O. Manadoperoxides A-D from the 

Indonesian sponge Plakortis cfr. simplex. Further insights on the structure-activity relationships 

of simple 1,2-dioxane antimalarials. J. Nat. Prod. 2010, 73, 1138-1145. 

94.  Mohammed, R.; Peng, J.; Kelly, M.; Yousaf, M.; Winn, E.; Odde, S.; Bie, Z.; Xie, A.; Doerksen, 

R.J.; Hamann, M.T. Polyketide-peroxides from a species of Jamaican Plakortis (Porifera: 

Demospongiae). Aust. J. Chem. 2010, 63, 877-885. 

95.  Jiménez-Romero, C.; Ortiz, I.; Vicente, J.; Vera, B.; Rodríguez, A.D.; Nam, S.; Jove, R. 

Bioactive cycloperoxides isolated from the Puerto Rican sponge Plakortis halichondrioides. J. 

Nat. Prod. 2010, 73, 1694-1700. 

96.  Ueoka, R.; Nakao, Y.; Kawatsu, S.; Yaegashi, J.; Matsumoto, Y.; Matsunaga, S.; Furihata, K.; 

van Soest, R.W.M.; Fusetani, N. Gracilioethers A−C, antimalarial metabolites from the marine 

sponge Agelas gracilis. J. Org. Chem. 2009, 74, 4203-4207. 

97.  Gutiérrez, M.; Tidgewell, K.; Capson, T.L.; Engene, N.; Almanza, A.; Schemies, J.; Jung, M.; 

Gerwick, W.H. Malyngolide dimer, a bioactive symmetric cyclodepside from the Panamanian 

marine cyanobacterium Lyngbya majuscula. J. Nat. Prod. 2010, 73, 709-711. 

98.  Kumari, P.; Misra, K.; Sisodia, B.S.; Faridi, U.; Srivastava, S.; Luqman, S.; Darokar, M.P.; Negi, 

A.S.; Gupta, M.M.; Singh, S.C.; Kumar, J.K. A promising anticancer and antimalarial component 

from the leaves of Bidens pilosa. Planta Med. 2009, 75, 59-61. 

99.  Tobinaga, S.; Sharma, M.K.; Aalbersberg, W.G.L.; Watanabe, K.; Iguchi, K.; Narui, K.; Sasatsu, 

M.; Waki, S. Isolation and identification of a potent antimalarial and antibacterial polyacetylene 

from Bidens pilosa. Planta Med. 2009, 75, 624-628. 

100. Gupta, P.; Vasudeva, N. In vitro antiplasmodial and antimicrobial potential of Tagetes erecta 

roots. Pharm. Biol. 2010, 48, 1218-1223. 

101. Xu, L.; He, Z.; Xue, J.; Chen, X.; Wei, X. β-Resorcylic acid lactones from a Paecilomyces 

fungus. J. Nat. Prod. 2010, 73, 885-889. 

102. Khumkomkhet, P.; Kanokmedhakul, S.; Kanokmedhakul, K.; Hahnvajanawong, C.; Soytong, K. 

Antimalarial and cytotoxic depsidones from the fungus Chaetomium brasiliense. J. Nat. Prod. 

2009, 72, 1487-1491. 

103. Marti, G.; Eparvier, V.; Moretti, C.; Susplugas, S.; Prado, S.; Grellier, P.; Retailleau, P.; Guéritte, 

F.; Litaudon, M. Antiplasmodial benzophenones from the trunk latex of Moronobea coccinea 

(Clusiaceae). Phytochemistry 2009, 70, 75-85. 



Molecules 2011, 16                            

 

 

2190

104. Marti, G.; Eparvier, V.; Moretti, C.; Prado, S.; Grellier, P.; Hue, N.; Thoison, O.; Delpech, B.; 

Guéritte, F.; Litaudon, M. Antiplasmodial benzophenone derivatives from the root barks of 

Symphonia globulifera (Clusiaceae). Phytochemistry 2010, 71, 964-974. 

105. Lane, A.L.; Stout, E.P.; Lin, A.S.; Prudhomme, J.; Le Roch, K.; Fairchild, C.R.; Franzblau, S.G.; 

Hay, M.E.; Aalbersberg, W.; Kubanek, J. Antimalarial bromophycolides J-Q from the Fijian red 

alga Callophycus serratus. J. Org. Chem. 2009, 74, 2736-2742. 

106. Kornsakulkarn, J.; Thongpanchang, C.; Chainoy, R.; Choowong, W.; Nithithanasilp, S.; 

Thongpanchang, T. Bioactive metabolites from cultures of basidiomycete Favolaschia 

tonkinensis. J. Nat. Prod. 2010, 73, 759-762. 

107. Bunyapaiboonsri, T.; Yoiprommarat, S.; Intereya, K.; Rachtawee, P.; Hywel-Jones, N.L.; Isaka, 

M. Isariotins E and F, spirocyclic and bicyclic hemiacetals from the entomopathogenic fungus 

Isaria tenuipes BCC 12625. J. Nat. Prod. 2009, 72, 756-759. 

108. Lebouvier, N.; Jullian, V.; Desvignes, I.; Maurel, S.; Parenty, A.; Dorin-Semblat, D.; Doerig, C.; 

Sauvain, M.; Laurent, D. Antiplasmodial activities of homogentisic acid derivative protein kinase 

inhibitors isolated from a Vanuatu marine sponge Pseudoceratina sp. Mar. Drugs 2009, 7,  

640-653. 

109. Moosophon, P.; Kanokmedhakul, S.; Kanokmedhakul, K.; Soytong, K. Prenylxanthones and a 

bicyclo [3.3.1]nona-2,6-diene derivative from the fungus Emericella rugulosa. J. Nat. Prod. 

2009, 72, 1442-1446. 

110. Chung, I.M.; Seo, S.H.; Kang, E.Y.; Park, W.H.; Moon, H.I. Anti-malarial activity of  

6-(8'Z-pentadecenyl)-salicylic acid from Viola websteri in mice. Malar. J. 2009, 8,151. 

111. Rangkaew, N.; Suttisri, R.; Moriyasu, M.; Kawanishi, K. A new acyclic diterpene acid and 

bioactive compounds from Knema glauca. Arch. Pharm. Res. 2009, 32, 685-692. 

© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article 

distributed under the terms and conditions of the Creative Commons Attribution license 

(http://creativecommons.org/licenses/by/3.0/).