Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India.
Centre for Advanced Materials & Industrial Chemistry (CAMIC), School of Science, RMIT University, GPO BOX 2476, Melbourne 3001, Australia.
Eur J Med Chem. 2017 Sep 29;138:234-245. doi: 10.1016/j.ejmech.2017.06.035. Epub 2017 Jun 23.
A series of new benzimidazole bearing thiazolidinedione derivatives has been designed, synthesized by using conventional as well as microwave-assisted methods. Microwave-assisted synthesis caused a significant reduction in the reaction times and improvement in the yields of all the derivatives. All the new synthesized compounds were evaluated for their in vitro cytotoxic potential against selected human cancer cell lines of breast (MDAMB-231), prostate (PC-3), cervical (HeLa), lung (A549) and bone (HT1080) along with a normal kidney cells (HeK-293T). The compounds 17n, 17p and 17q were found to be potent cytotoxic with IC values in the range of 0.096-0.63 μM on PC-3, HeLa, A549 and HT1080 cancer cells. Most of the compounds have found to be safe on normal HeK-293T kidney cells in comparison to cancer cells. The treatment of cells with 17p and 17q showed the typical apoptotic morphological features like fragmentation and shrinkage of nuclei. Further, test compounds resulted in inhibition of cell migration through disruption of F-actin protein assembly. Hoechst, DCFH-DA staining, mitochondrial membrane and annexin binding assays revealed that the cancer cell proliferation was inhibited through induction of apoptosis in A549 cells.
一系列新的含苯并咪唑的噻唑烷二酮衍生物已经被设计并通过常规和微波辅助方法合成。微波辅助合成显著地减少了反应时间并提高了所有衍生物的产率。所有新合成的化合物都被评估了对选定的人乳腺癌（MDAMB-231）、前列腺癌（PC-3）、宫颈癌（HeLa）、肺癌（A549）和骨癌（HT1080）以及正常肾细胞（HeK-293T）的体外细胞毒性潜力。化合物 17n、17p 和 17q 被发现对 PC-3、HeLa、A549 和 HT1080 癌细胞具有很强的细胞毒性，IC 值在 0.096-0.63 μM 范围内。与癌细胞相比，大多数化合物在正常的 HeK-293T 肾细胞中被发现是安全的。用 17p 和 17q 处理细胞显示出典型的凋亡形态特征，如核的碎裂和收缩。此外，测试化合物通过破坏 F-肌动蛋白蛋白组装来抑制细胞迁移。Hoechst、DCFH-DA 染色、线粒体膜和膜联蛋白结合实验表明，通过诱导 A549 细胞凋亡，癌细胞增殖受到抑制。
