Blau, Lorena [UNESP]Menegon, Renato FarinaTrossini, Gustavo H. G.Molino, João Vitor DutraVital, Drielli GomesCicarelli, Regina Maria Barretto [UNESP]Passerini, Gabriela Duó [UNESP]Bosquesi, Priscila Longhin [UNESP]Chin, Chung Man [UNESP]2014-05-272014-05-272013-08-27European Journal of Medicinal Chemistry, v. 67, p. 142-151.0223-52341768-3254http://hdl.handle.net/11449/76337The present work reports on the synthesis, biological assaying and docking studies of a series of 12 aryl thiosemicarbazones, which were planned to act over two main enzymes, cruzain and trypanothione reductase. These enzymes are used as targets of trypanocidal activity in Chagas disease control with a minimal mutagenic profile. Three p-nitroaromatic thiosemicarbazones showed high activity against Trypanosoma cruzi in in vitro assays (IC50 < 57 μM), and no mutagenic profile was observed in micronucleous tests. Although the in vitro inhibition test showed that 10-μM doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity. © 2013 Elsevier Masson SAS. All rights reserved.142-151engChagas diseaseCruzainDockingMutagenicityOxidative stressThiosemicarbazone2 amino 1 (3 nitrophenyl)ethan 1 one thiosemicarbazone2 amino 1 (4 nitro) acetophenone thiosemicarbazone hemisuccinate amide2 amino 1 (4 nitro)acetophenone thiosemicarbazone2 amino 1 phenylethan 1 one thiosemicarbazone2 hidroxy 1 (4 nitro) acetophenone thiosemicarbazone hemisuccinate ester2 hydroxy 1 (4 nitro)acetophenone thiosemicarbazone3 amino 4 nitroacetophenone thiosemicarbazone3 nitro 4 aminoacetophenone thiosemicarbazone4 aminoacetophenone thiosemicarbazoneacetophenone thiosemicarbazoneaminoacetophenone thiosemicarbazoneantiprotozoal agentcruzipainthiosemicarbazone derivativetrypanothione reductaseunclassified drugantiprotozoal activitybiological activitybrominationconcentration responsedrug designdrug mechanismdrug structuredrug synthesisIC 50in vitro studymelting pointmolecular dockingmutagenic activitymutagenicitynonhumantrypanocidal activityTrypanosoma cruziDesign, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidatesArtigo10.1016/j.ejmech.2013.04.022WOS:000325121800016Acesso restrito2-s2.0-8488252832497343336079754130000-0003-4141-0455