Palkar Mahesh B, Jalalpure Sunil S, Rane Rajesh A, Patel Harun M, Shaikh Mahamadhanif S, Hampannavar Girish A, Alwan Wesam S, Bolakatti Girish S, Karpoormath Rajshekhar
Department of Pharmaceutical Chemistry, K.L.E. University College of Pharmacy, Vidyanagar, Hubballi-580 031, Karnataka, India.
Anticancer Agents Med Chem. 2015;15(8):970-9. doi: 10.2174/1871520615666150424110339.
In this research work, a series of eighteen novel coumarinyl substituted thiazolidin-2,4-dione analogs (4a-4r) have been designed by molecular hybridization approach, synthesized and their structures were established on the basis of FTIR, 1H NMR, 13C NMR and elemental (CHN) analysis. These title compounds were screened for their cytotoxicity using MTT assay methodology against five different mammalian cancer cell lines viz. hormone dependant breast adenocarcinoma (MCF7), cervical carcinoma (HeLa), colorectal carcinoma (HT29), lung cancer (A549) and prostate adeno carcinoma (PC3). The cytotoxicity screening studies revealed that MCF-7, HeLa and A549 cancer cell lines were sensitive to all the tested compounds. Though the compounds showed varying degrees of cytotoxicity in the tested cell lines, most significant effect was observed for compounds 4i (1.06, 2.4 and 3.06 µM) and 4o (0.95, 3.2 and 2.38 μM) against MCF7, HeLa and A549 cell lines respectively. In conclusion, the anticancer results of these promising leads strongly encouraged us for additional lead optimization with the aim of developing more potential anticancer agents.
在本研究工作中，通过分子杂交方法设计并合成了一系列18种新型香豆素基取代的噻唑烷 - 2,4 - 二酮类似物（4a - 4r），并基于傅里叶变换红外光谱（FTIR）、核磁共振氢谱（1H NMR）、核磁共振碳谱（13C NMR）和元素（CHN）分析确定了它们的结构。使用MTT法对这些目标化合物针对五种不同的哺乳动物癌细胞系进行细胞毒性筛选，这五种细胞系分别为激素依赖性乳腺腺癌（MCF7）、子宫颈癌（HeLa）、结肠直肠癌（HT29）、肺癌（A549）和前列腺腺癌（PC3）。细胞毒性筛选研究表明，MCF - 7、HeLa和A549癌细胞系对所有测试化合物均敏感。尽管这些化合物在测试细胞系中表现出不同程度的细胞毒性，但分别对MCF7、HeLa和A549细胞系而言，化合物4i（1.06、2.4和3.06 μM）和4o（0.95、3.2和2.38 μM）的效果最为显著。总之，这些有前景的先导化合物的抗癌结果极大地鼓舞了我们进行进一步的先导优化，以期开发出更具潜力的抗癌药物。
