Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
Department of Natural Sciences, University of Houston - Downtown, Houston, TX 77002, United States.
Eur J Med Chem. 2017 Aug 18;136:184-194. doi: 10.1016/j.ejmech.2017.04.078. Epub 2017 May 3.
A novel series of ketohydrazide-hydrazones as analogues of naturally occurring coscinamides has been synthesized and evaluated for their anticancer activity against five cancer cell lines. Of the twenty-synthesized ketohydrazide-hydrazones, compounds, 21c, 21f, 21g, 21k and 21o showed cytotoxic effects (less than 50% cell survival) against multiple cancer cell lines when tested at a final concentration of 10 μM. IC of three compounds 21f, 21k and 21o was determined to be less than 5 μM for all tested cancer cell lines. Compound 21k exhibited significant anticancer activity against MCF-7, MDA-MB-231, HCT-116 and JURKAT cancer cell lines with IC values of 0.8 μM, 0.50 μM, 0.15 μM, and 0.22 μM, respectively. Also, 21k was found to be more selectively cytotoxic against tumor cells when compared to normal cells. Preliminary mechanism of action studies indicated that the most active compound 21k induced caspase-dependent apoptosis in cells. 21k arrests cell cycle in G2/M phase by inhibiting of tubulin polymerization (IC = 0.6 μM).
已经合成了一系列新型的酮腙-腙类似物作为天然存在的柯西酰胺的类似物，并对其针对五种癌细胞系的抗癌活性进行了评估。在所合成的二十个酮腙-腙中，当终浓度为 10μM 时，化合物 21c、21f、21g、21k 和 21o 对多种癌细胞系表现出细胞毒性作用（细胞存活率低于 50%）。三种化合物 21f、21k 和 21o 的 IC 在所有测试的癌细胞系中均小于 5μM。化合物 21k 对 MCF-7、MDA-MB-231、HCT-116 和 JURKAT 癌细胞系表现出显著的抗癌活性，IC 值分别为 0.8μM、0.50μM、0.15μM 和 0.22μM。此外，与正常细胞相比，21k 对肿瘤细胞的细胞毒性更具选择性。初步作用机制研究表明，最活跃的化合物 21k 在细胞中诱导了 caspase 依赖性细胞凋亡。21k 通过抑制微管蛋白聚合将细胞周期阻滞在 G2/M 期（IC=0.6μM）。
