Design, synthesis and biological evaluation of new aryl thiosemicarbazone as antichagasic candidates

Author(s)

Blau, Lorena ^[1] ; Menegon, Renato Farina ^[2] ; Trossini, Gustavo H. G. ^[3] ; Dutra Molino, Joao Vitor ^[3] ; Vital, Drielli Gomes ^[3] ; Barretto Cicarelli, Regina Maria ^[4] ; Passerini, Gabriela Duo ^[4] ; Bosquesi, Priscila Longhin ^[1] ; Chin, Chung Man ^[1]

Affiliation

^[1] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Farmacos & Med, BR-14801902 Araraquara, SP - Brazil

^[2] Univ Vale Paraiba, Inst Pesquisa & Desenvolvimento, BR-12244000 Sao Jose Dos Campos, SP - Brazil

^[3] Univ Sao Paulo, Fac Ciencias Farmaceut, Dept Farm, BR-05508900 Sao Paulo - Brazil

^[4] Univ Estadual Paulista, Fac Ciencias Farmaceut, Dept Ciencias Biol, BR-14801902 Araraquara, SP - Brazil

• Document type: Journal article
• Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 67, p. 142-151, SEP 2013.
• Web of Science Citations: 20

Abstract

The 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 Ttypanosoma cruzi in in vitro assays (IC50 < 57 mu M), and no mutagenic profile was observed in micro-nucleous tests. Although the in vitro inhibition test showed that 10-mu M doses of eight compounds inhibited cruzain activity, no correlation was found between cruzain inhibition and trypanocidal activity. (C) 2013 Elsevier Masson SAS. All rights reserved. (AU)

• FAPESP's process: 11/11499-0 - Bioisosterism in the design of new antichagasic agents: integration of computational and experimental strategies
• Grantee: Gustavo Henrique Goulart Trossini
• Support type: Regular Research Grants