Convergent synthesis and cruzain inhibitory activity of novel 2-(N

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• 作者：Nilo Zanatta ; Simone S. Amaral ; Josiane M. dos Santos ; Dé ; bora L. de Mello ; Liana da S. Fern ; es ; Helio G. Bonacorso ; Marcos A.P. Martins ; Adriano D. Andricopulo ; Deise M. Borchhardt
• 关键词：Benzylidenehydrazino ; Trifluoromethyl pyrimidines ; Pyrimidines ; Enones ; Cruzain Inhibitory Activity
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 December 2008
• 年：2008
• 卷：16
• 期：24
• 页码：10236-10243
• 全文大小：302 K

文摘

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 μM) and IC₅₀ value (85 μM) 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.