Stilbene鈥揅halcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis

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• 作者：Naina Sharma ; Dinesh Mohanakrishnan ; Amit Shard ; Abhishek Sharma ; Saima ; Arun K. Sinha ; Dinkar Sahal
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：January 12, 2012
• 年：2012
• 卷：55
• 期：1
• 页码：297-311
• 全文大小：783K
• 年卷期：v.55,no.1(January 12, 2012)
• ISSN：1520-4804

文摘

Novel stilbene鈥揷halcone (S-C) hybrids were synthesized via a sequential Claisen鈥揝chmidt鈥揔noevenagel鈥揌eck approach and evaluated for antiplasmodial activity in in vitro red cell culture using SYBR Green I assay. The most potent hybrid (11) showed IC₅₀ of 2.2, 1.4, and 6.4 渭M against 3D7 (chloroquine sensitive), Indo, and Dd2 (chloroquine resistant) strains of Plasmodium falciparum, respectively. Interestingly, the respective individual stilbene (IC₅₀ > 100 渭M), chalcone (IC₅₀ = 11.5 渭M), or an equimolar mixture of stilbene and chalcone (IC₅₀ = 32.5 渭M) were less potent than 11. Studies done using specific stage enriched cultures and parasite in continuous culture indicate that 11 and 18 spare the schizont but block the progression of the parasite life cycle at the ring or the trophozoite stages. Further, 11 and 18 caused chromatin condensation, DNA fragmentation, and loss of mitochondrial membrane potential in Plasmodium falciparum, thereby suggesting their ability to cause apoptosis in malaria parasite.