Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores

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• 作者：Koneni V. Sashidhara^a ; ^{kv_sashidhara@cdri.res.in} ; ^{sashidhar123@gmail.com} ; Manoj Kumar^a ; Ram K. Modukuri^a ; Rajeev Kumar Srivastava^b ; Awakash Soni^b ; Kumkum Srivastava^b ; Shiv Vardan Singh^c ; J.K. Saxena^c ; Harsh M. Gauniyal^d ; Sunil K. Puri^b
• 关键词：Synthesis ; Quinoline ; Keto-enamine ; Antimalarial agents
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：1 May, 2012
• 卷：20
• 期：9
• 页码：2971-2981
• 文件大小：2393 K

摘要

A series of novel keto-enamine chalcone-chloroquine based hybrids were synthesized following new methodology developed in our laboratory. The synthesized compounds were screened against chloroquine sensitive strain (3D7) of Plasmodium falciparum in an in vitro model. Some of the compounds were showing comparable antimalarial activity at par with chloroquine. Compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in Swiss mice against Plasmodium yoelii (chloroquine resistant N-67 strain), wherein compounds 25 and 27 each showed an in vivo suppression of 99.9%parasitaemia on day 4. Biochemical studies reveal that inhibition of hemozoin formation is the primary mechanism of action of these analogues.