Article
Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents
Registro en:
HERNANDES, M. Z. et al. Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents. Bioorganic & Medicinal Chemistry, v. 18, n. 22, p. 7826–7835, 15 nov. 2010.
1464-3391
10.1016/j.bmc.2010.09.056
Autor
Hernandes, Marcelo Zaldini
Rabello, Marcelo Montenegro
Leite, Ana Cristina Lima
Cardoso, Marcos Veríssimo Oliveira
Moreira, Diogo Rodrigo Magalhaes
Brondani, Dalci José
Simone, Carlos Alberto
Reis, Luiza Campos
Souza, Marina Assis
Pereira, Valéria Rego Alves
Ferreira, Rafaela Salgado
McKerrow, James Hobson
Resumen
Esta pesquisa recebeu apoio da Fundação Estadual de Ciência e Tecnologia de Pernambuco (FACEPE, outorga nº APQ-0123-4.03 / 08 ) e do Conselho Nacional de Pesquisa (CNPq, outorga nº 472880 / 2009-8 ). In previous studies, we identified promising anti-Trypanosoma cruzi cruzain inhibitors based on thiazolylhydrazones. To optimize this series, a number of medicinal chemistry directions were explored and new thiazolylhydrazones and thiosemicarbazones were thus synthesized. Potent cruzain inhibitors were identified, such as thiazolylhydrazones 3b and 3j, which exhibited IC(50) of 200-400nM. Furthermore, molecular docking studies showed concordance with experimentally derived structure-activity relationships (SAR) data. In the course of this work, lead compounds exhibiting in vitro activity against both the epimastigote and trypomastigote forms of T. cruzi were identified and in vivo general toxicity analysis was subsequently performed. Novel SAR were documented, including the importance of the thiocarbonyl carbon attached to the thiazolyl ring and the direct comparison between thiosemicarbazones and thiazolylhydrazones. 2050-01-01
Materias
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