TY - JOUR
T1 - Stilbene-chalcone hybrids
T2 - Design, synthesis, and evaluation as a new class of antimalarial scaffolds that trigger cell death through stage specific apoptosis
AU - Sharma, Naina
AU - Mohanakrishnan, Dinesh
AU - Shard, Amit
AU - Sharma, Abhishek
AU - Saima,
AU - Sinha, Arun K.
AU - Sahal, Dinkar
PY - 2012/1/12
Y1 - 2012/1/12
N2 - 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 IC 50 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 (IC 50 > 100 μM), chalcone (IC 50 = 11.5 μM), or an equimolar mixture of stilbene and chalcone (IC 50 = 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.
AB - 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 IC 50 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 (IC 50 > 100 μM), chalcone (IC 50 = 11.5 μM), or an equimolar mixture of stilbene and chalcone (IC 50 = 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.
UR - http://www.scopus.com/inward/record.url?scp=84863411418&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84863411418&partnerID=8YFLogxK
U2 - 10.1021/jm201216y
DO - 10.1021/jm201216y
M3 - Article
C2 - 22098429
AN - SCOPUS:84863411418
SN - 0022-2623
VL - 55
SP - 297
EP - 311
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 1
ER -