Convergent synthesis and cruzain inhibitory activity of novel 2-(N'-benzylidenehydrazino)-4-trifluoromethyl-pyrimidines |
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Authors: | Zanatta Nilo Amaral Simone S Dos Santos Josiane M de Mello Débora L Fernandes Liana da S Bonacorso Helio G Martins Marcos A P Andricopulo Adriano D Borchhardt Deise M |
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Institution: | Núcleo de Química de Heterociclos (NUQUIMHE), Departamento de Química, Universidade Federal de Santa Maria, 97.105-900 Santa Maria, RS, Brazil. zanatta@base.ufsm.br |
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Abstract: | 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 microM) and IC(50) value (85 microM) 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. |
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