| Autor: |
dos Santos Filho JM; Departamento de Engenharia Química, Centro de Tecnologia e Geociências, Universidade Federal de Pernambuco, Rua Prof. Artur Sá S/N, Cidade Universitária, 50740-521 Recife, PE, Brazil. mauricio_santosfilho@yahoo.com.br, Leite AC, de Oliveira BG, Moreira DR, Lima MS, Soares MB, Leite LF |
| Jazyk: |
angličtina |
| Zdroj: |
Bioorganic & medicinal chemistry [Bioorg Med Chem] 2009 Sep 15; Vol. 17 (18), pp. 6682-91. Date of Electronic Publication: 2009 Aug 06. |
| DOI: |
10.1016/j.bmc.2009.07.068 |
| Abstrakt: |
Research in recent years has demonstrated that the Trypanosoma cruzi cysteine protease cruzain (TCC) is a valid chemotherapeutic target, since inhibitors of this protease affect the pathology appropriately. By exploring the N-acylhydrazones (NAH) as privileged structures usually present in antiparasitic agents, we investigated a library of 16 NAH bearing the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold (NAH 3a-h, 4a-h). The in vitro bioactivity against epimastigote and trypomastigote forms of T. cruzi was evaluated, and some NAH under study exhibited antitrypanosomal activity at concentrations that are not toxic to mammalian cells. The series of compounds based on the 3-(4-substituted-aryl)-1,2,4-oxadiazole scaffold revealed the remarkable importance of each substituent at the phenyl's 4-position for the inhibitory activity. Non-nitrated compounds 3a and 4e were found to be as potent as the reference drug, Benznidazole. In addition, the molecular origin of the antitrypanosomal properties for these series was investigated using docking studies of the TCC structure. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect