Li Yu-Jing, Qin Ya-Juan, Makawana Jigar A, Wang Yan-Ting, Zhang Yan-Qing, Zhang Ya-Liang, Yang Meng-Ru, Jiang Ai-Qin, Zhu Hai-Liang
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China; School of Medicine, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2014 Aug 1;22(15):4312-22. doi: 10.1016/j.bmc.2014.05.017. Epub 2014 May 17.
A series of 1,3,4-thiadiazol-2-amide derivatives (6a-w) were designed and synthesized as potential inhibitors of tubulin polymerization and as anticancer agents. The in vitro anticancer activities of these compounds were evaluated against three cancer cell lines by the MTT method. Among all the designed compounds, compound 6f exhibited the most potent anticancer activity against A549, MCF-7 and HepG2 cancer cell lines with IC₅₀ values of 0.03 μM, 0.06 μM and 0.05 μM, respectively. Compound 6f also exhibited significant tubulin polymerization inhibitory activity (IC₅₀=1.73 μM), which was superior to the positive control. The obtained results, along with a 3D-QSAR study and molecular docking that were used for investigating the probable binding mode, could provide an important basis for further optimization of compound 6f as a novel anticancer agent.
设计并合成了一系列1,3,4-噻二唑-2-酰胺衍生物（6a-w），作为微管蛋白聚合的潜在抑制剂和抗癌剂。采用MTT法评估了这些化合物对三种癌细胞系的体外抗癌活性。在所有设计的化合物中，化合物6f对A549、MCF-7和HepG2癌细胞系表现出最强的抗癌活性，IC₅₀值分别为0.03 μM、0.06 μM和0.05 μM。化合物6f还表现出显著的微管蛋白聚合抑制活性（IC₅₀ = 1.73 μM），优于阳性对照。所获得的结果，连同用于研究可能结合模式的3D-QSAR研究和分子对接，可为进一步优化化合物6f作为新型抗癌剂提供重要依据。
