Produção Nacional
Revisado por pares
Studies toward the structural optimization of novel thiazolylhydrazone-based potent antitrypanosomal agents
2010; Elsevier BV; Volume: 18; Issue: 22 Linguagem: Inglês
10.1016/j.bmc.2010.09.056
ISSN1464-3391
AutoresMarcelo Zaldini Hernandes, Marcelo Montenegro Rabello, Ana Cristina Lima Leite, Marcos Veríssimo de Oliveira Cardoso, Diogo Rodrigo Magalhães Moreira, Dalci José Brondani, Carlos A. de Simone, Luiza Campos Reis, Marina de Assis Souza, Valéria Rêgo Alves Pereira, Rafaela Salgado Ferreira, James H. McKerrow,
Tópico(s)Bioactive Compounds and Antitumor Agents
ResumoIn 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.
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