Convergent synthesis and cruzain inhibitory activity of novel 2-(N `-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2008
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Resumo |
To search for new cruzain inhibitors, the synthesis of a series of novel 2-(N`-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines in a convergent manner is presented. The cruzain inhibitory activity of some of these compounds was evaluated and a binding model was proposed. All derivatives tested were active and the most significant inhibitory effect (80% at 100 mu M) and IC(50) value (85 mu M) were obtained from the 2-(N`-4-chloro-benzylidenehydrazino)-4-trifluoromethyl-pyrimidine. Although further structural optimization to improve solubility is necessary, the molecular docking studies suggest that these inhibitors occupy the S2 pocket without irreversible enzyme inactivation, through hydrophobic interactions, thus, indicating a desirable mode of interaction for the design of novel inhibitors. (C) 2008 Elsevier Ltd. All rights reserved. CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)[477682/01-4] Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP (Fundacao de Amparo a Pesquisa de Estado de Sao Paulo) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) FAPESP |
Identificador |
BIOORGANIC & MEDICINAL CHEMISTRY, v.16, n.24, p.10236-10243, 2008 0968-0896 http://producao.usp.br/handle/BDPI/29982 10.1016/j.bmc.2008.10.052 |
Idioma(s) |
eng |
Publicador |
PERGAMON-ELSEVIER SCIENCE LTD |
Relação |
Bioorganic & Medicinal Chemistry |
Direitos |
restrictedAccess Copyright PERGAMON-ELSEVIER SCIENCE LTD |
Palavras-Chave | #Benzylidenehydrazino #Trifluoromethyl pyrimidines #Pyrimidines #Enones #Cruzain Inhibitory Activity #TRYPANOSOMA-CRUZI #CHAGAS-DISEASE #DERIVATIVES #DOCKING #DESIGN #POTENT #AGENTS #AMINOGUANIDINE #PYRIMIDINES #CONVENIENT #Biochemistry & Molecular Biology #Chemistry, Medicinal #Chemistry, Organic |
Tipo |
article original article publishedVersion |