Design, synthesis and biological evaluation of 2-substituted quinolines as potential antileishmanial agents

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• 作者：Vadiraj S. Gopinath ; Jakir Pinjari ; Ravindra T. Dere ; Aditya Verma ; Preeti Vishwakarma ; Rahul Shivahare ; Manjunath Moger ; Palusa Sanath Kumar Goud ; Vikram Ramanathan ; Prosenjit Bose ; M.V.S. Rao ; Suman Gupta ; Sunil K. Puri ; Delphine Launay ; Denis Martin
• 关键词：2-Substituted quinolines ; Antileishmanial activity ; Luciferase assay ; Liver microsomes ; Metabolic stability
• 刊名：European Journal of Medicinal Chemistry
• 出版年：November, 2013
• 年：2013
• 卷：69
• 期：Complete
• 页码：527-536
• 全文大小：1159 K

文摘

An analogous library of 2-substituted quinoline compounds was synthesized with the aim to identify a potential drug candidate to treat visceral leishmaniasis. These molecules were tested for their in聽vitro and in聽vivo biological activity against Leishmania donovani. Metabolic stability of these compounds was also improved through the introduction of halogen substituents. Compound (26g), found to be the most active; exhibited an IC₅₀ value of 0.2聽渭M and >180 fold selectivity. The hydrochloride salt of (26g) showed 84.26聽卤聽4.44 percent inhibition at 50聽mg/kg聽脳聽5聽days (twice daily, oral route) dose in L.聽donovani/hamster model. The efficacy was well correlated with the PK data observed which indicating that the compound is well distributed.