Synthesis of imidazo[2,1-b][1,3,4]thiadiazole–chalcones as apoptosis inducing anticancer agents
Synthesis of imidazo[2,1-b][1,3,4]thiadiazole–chalcones as apoptosis inducing anticancer agents
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DOI：
10.1039/c4md00228h
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发表时间：
2014-10
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影响因子：
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通讯作者：
A. Kamal;V. S. Reddy;K. Santosh;Gajjela Bharath Kumar;A. B. Shaik;R. Mahesh;Sumit Chourasiya;I. Sayeed;S. Kotamraju
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文献类型：
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作者：
A. Kamal;V. S. Reddy;K. Santosh;Gajjela Bharath Kumar;A. B. Shaik;R. Mahesh;Sumit Chourasiya;I. Sayeed;S. Kotamraju
通过Claisen-Schmidt缩合反应合成了一系列新的咪唑并[2，1-B][1，3，4]噻二唑-查尔酮化合物，并评价了它们对多种人癌细胞系的细胞毒活性。这些化合物显示出中等至可观的抗增殖活性。有趣的是，化合物11 a和11b在某些癌细胞系中表现出显著的细胞毒性活性，IC 50值范围为0.65至2.25 μM。构效关系（SAR）研究表明，含3，4，5-三甲氧基的化合物对选定的癌细胞系显示出上级其他查耳酮的细胞毒活性。这些化合物在DU-145细胞中显示G 0/G1期阻滞，除了半胱天冬酶-3和8的激活。这些化合物的生长抑制作用与细胞周期调节蛋白cyclin D1的减少和细胞周期蛋白依赖性激酶抑制剂如Cip 1/p21和Kip 1/p27的增加有关。
A series of new imidazo[2,1-b][1,3,4]thiadiazole–chalcones were synthesized by Claisen–Schmidt condensation and evaluated for their cytotoxic activity against various human cancer cell lines. These compounds showed moderate to appreciable antiproliferative activities. Interestingly, compounds like 11a and 11b exhibited significant cytotoxic activity with IC50 values ranging from 0.65 to 2.25 μM in certain cancer cell lines. The structure–activity relationship (SAR) studies reveal that 3,4,5-trimethoxy group containing compounds showed superior cytotoxic activity against selected cancer cell lines compared to other chalcones. These compounds showed G0/G1 phase arrest, apart from activation of caspase-3 and 8 in DU-145 cells. The growth inhibitory effect of these compounds was associated with a decrease in cell cycle regulatory protein cyclin D1 and increase in cyclin dependent kinase inhibitors like Cip1/p21 and Kip1/p27.