Atividade antimicrobiana de aminochalconas contra células planctônicas e biofilmes
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Data
2021-11-24
Autores
Garcia, Mayara Aparecida Rocha
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Universidade Estadual Paulista (Unesp)
Resumo
As infecções nosocomiais são uma das principais causas de mortalidade em todo mundo. O surgimento de agentes antimicrobianos inovadores vem se tornando uma necessidade, uma vez que as altas taxas de infecções são devidas ao aumento da resistência bacteriana. Este trabalho teve como objetivo a síntese de aminochalconas e sua avaliação contra Staphyloccous aureus e Candida albicans, sendo determinados os valores de concentração inibitória mínima (CIM), concentração bactericida mínima (CBM) e concentração fungicida mínima (CFM). As aminochalconas foram sintetizadas por reação de condensação aldólica de Claisen-Schmidt em catálise básica. A potencialização do efeito antimicrobiano das aminochalconas foi alcançada por meio do emprego do Método Manual de Topliss, o qual preconiza substituintes em anéis aromáticos, segundo seus efeitos estereoeletrônicos e hidrofobicidade. A chalcona 3f (3’-amino-4-bromochalcona) mais ativa contra S. aureus sensível e resistente à meticilina (MSSA e MRSA) exibiu CIM de 1,95 μg/mL para MSSA e 7,80 μg/mL para MRSA, foi selecionada para avaliação da sua combinação com antibióticos, atividade anti-adesão, antibiofilme e toxicidade in vivo usando larvas de Gallera mellonella. Além disso, as aminochalconas foram avaliadas quanto a atividade antibacteriana contra outras espécies e Mycobacterium tuberculosis. O tratamento com 3f diminuiu a adesão de MSSA e MRSA aos queratinócitos humanos, além de atividade antibiofilme similar à vancomicina. Demonstrou baixa toxicidade a 10 × CIM após 72 horas, com morte de 20% das larvas de G. mellonella. A aminochalcona mais ativa contra Candida albicans também foi selecionada para avaliação antibiofilme, anti-adesão, e tempo de morte desse fungo, além do estudo de mecanismo de ação e toxicidade em G. mellonella. A chalcona 3n (3’amino-3-fluorchalcona) demonstrou CIM de 3,90 μg/mL contra C. albicans e foi selecionada para os ensaios posteriores, demonstrando ação fungicida no ensaio de tempo-morte. Demonstrou atividade antibiofilme e anti-adesão similar a anfotericina B. Além disso, 3n demonstrou interação com ergosterol de membrana, sendo um possível mecanismo de ação dessa chalcona. A baixa toxicidade a 100 × CIM foi responsável pela morte de 20% das larvas de G. mellonella.
Nosocomial infections are one of the main causes of mortality worldwide. The emergence of innovative antimicrobial agents is becoming a necessity, since the high rates are due to the increase in bacterial resistance. The objective of this work was the synthesis of aminochalcones and their evaluation against Staphyloccous aureus and Candida albicans, being determined the values of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). Aminochalcones were synthesized by the Claisen-Schmidt aldol condensation reaction in basic catalysis. The potentiation of the antimicrobial effect of aminochalcones was achieved through the use of the Topliss’ Manual Method, which recommends substituents in aromatic rings, according to their stereoelectronic effects and hydrophobicity. Chalcone 3f (3’-amino4-bromochalcone) more active against methicillin-sensitive and resistant S. aureus (MSSA and MRSA) exhibited MIC of 1.95 µg/mL for MSSA and 7.80 µg/mL for MRSA, was selected for evaluation of its combination with antibiotics, anti-adhesion activity, anti-biofilm and in vivo toxicity using Gallera mellonella larvae. In addition, aminochalcones were evaluated for antibacterial activity against other species and Mycobacterium tuberculosis. Treatment with 3f decreased the adhesion of MSSA and MRSA to human keratinocytes, in addition to antibiofilm activity similar to vancomycin. It demonstrated low toxicity at 10 × MIC after 72 hours, with 20% death of G. mellonella larvae. The most active aminochalcone against Candida albicans was also referred for anti-biofilm, anti-adhesion, and time of death evaluation of this fungus, in addition to the study of its mechanism of action and toxicity in G. mellonella. Chalcone 3n (3'amino-3-fluorochalcone) demonstrated MIC of 3.90 µg/mL against C. albicans and was selected on to further tests, demonstrating fungicidal action in the time-death test. It demonstrated anti-biofilm and anti-adhesion activity similar to amphotericin B. In addition, sophisticated 3n with membrane ergosterol, being a possible mechanism of action of this chalcone. Low toxicity at 100 × MIC was responsible for the death of 20% of G. mellonella larvae
Nosocomial infections are one of the main causes of mortality worldwide. The emergence of innovative antimicrobial agents is becoming a necessity, since the high rates are due to the increase in bacterial resistance. The objective of this work was the synthesis of aminochalcones and their evaluation against Staphyloccous aureus and Candida albicans, being determined the values of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and minimum fungicidal concentration (MFC). Aminochalcones were synthesized by the Claisen-Schmidt aldol condensation reaction in basic catalysis. The potentiation of the antimicrobial effect of aminochalcones was achieved through the use of the Topliss’ Manual Method, which recommends substituents in aromatic rings, according to their stereoelectronic effects and hydrophobicity. Chalcone 3f (3’-amino4-bromochalcone) more active against methicillin-sensitive and resistant S. aureus (MSSA and MRSA) exhibited MIC of 1.95 µg/mL for MSSA and 7.80 µg/mL for MRSA, was selected for evaluation of its combination with antibiotics, anti-adhesion activity, anti-biofilm and in vivo toxicity using Gallera mellonella larvae. In addition, aminochalcones were evaluated for antibacterial activity against other species and Mycobacterium tuberculosis. Treatment with 3f decreased the adhesion of MSSA and MRSA to human keratinocytes, in addition to antibiofilm activity similar to vancomycin. It demonstrated low toxicity at 10 × MIC after 72 hours, with 20% death of G. mellonella larvae. The most active aminochalcone against Candida albicans was also referred for anti-biofilm, anti-adhesion, and time of death evaluation of this fungus, in addition to the study of its mechanism of action and toxicity in G. mellonella. Chalcone 3n (3'amino-3-fluorochalcone) demonstrated MIC of 3.90 µg/mL against C. albicans and was selected on to further tests, demonstrating fungicidal action in the time-death test. It demonstrated anti-biofilm and anti-adhesion activity similar to amphotericin B. In addition, sophisticated 3n with membrane ergosterol, being a possible mechanism of action of this chalcone. Low toxicity at 100 × MIC was responsible for the death of 20% of G. mellonella larvae
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Palavras-chave
Chalcona, Antimicrobiano, Biofilme, Chalcone, Antimicrobial, Biofilm