Stilbene−Chalcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis
IR@CSIR-IHBT
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Title |
Stilbene−Chalcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis |
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Creator |
Sharma, N
Mohanakrishan, Dinesh Shard, A Sharma , A ---, Saima Sinha, Arun K Sahal, D |
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Subject |
Plant sciences
Natural Product Chemistry |
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Description |
Novel stilbene−chalcone (S-C) hybrids were synthesized via a sequential Claisen−Schmidt−Knoevenagel− Heck 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 μM against 3D7 (chloroquine sensitive), Indo, and Dd2 (chloroquine resistant) strains of Plasmodium falciparum, respectively. Interestingly, the respective individual stilbene (IC50 > 100 μM), chalcone (IC50 = 11.5 μM), or an equimolar mixture of stilbene and chalcone (IC50 = 32.5 μM) 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. |
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Date |
2012
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Type |
Article
PeerReviewed |
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Format |
application/pdf
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Identifier |
http://ihbt.csircentral.net/1052/1/63_Stilbene-Chalcone_2012.pdf
Sharma, N and Mohanakrishan, Dinesh and Shard, A and Sharma , A and ---, Saima and Sinha, Arun K and Sahal, D (2012) Stilbene−Chalcone Hybrids: Design, Synthesis, and Evaluation as a New Class of Antimalarial Scaffolds That Trigger Cell Death through Stage Specific Apoptosis. Journal of Medicinal Chemistry, 55. pp. 297-311. |
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Relation |
http://ihbt.csircentral.net/1052/
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