Antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores |
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Authors: | Sashidhara Koneni V Kumar Manoj Modukuri Ram K Srivastava Rajeev Kumar Soni Awakash Srivastava Kumkum Singh Shiv Vardan Saxena J K Gauniyal Harsh M Puri Sunil K |
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Affiliation: | Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226 001, India. kv_sashidhara@cdri.res.in |
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Abstract: | 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. |
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