Li Yan-Hong, Zhang Bei, Yang Hai-Kui, Li Qiu, Diao Peng-Cheng, You Wen-Wei, Zhao Pei-Liang
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Eur J Med Chem. 2017 Jan 5;125:1098-1106. doi: 10.1016/j.ejmech.2016.10.051. Epub 2016 Oct 24.
Thirty-two novel 3-alkylsulfanyl-1,2,4-triazole derivatives, designed as cis-restricted combretastatin A-4 analogues, were synthesized and evaluated for their antiproliferative activities. The results indicated that analogue 20 showed more potent antiproliferative activities against PC-3 cell lines than positive control CA-4. Particularly, the most promising compound 25 displayed 5-fold improvement compared to CA-4 in inhibiting HCT116 cell proliferation with IC values of 1.15 μM. Further flow-activated cell sorting analysis revealed that compound 20 displayed a significant effect on G/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. From this study, analogues 20 and 25 were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.
设计合成了32种新型的3-烷硫基-1,2,4-三唑衍生物，作为顺式受限的康普瑞汀A-4类似物，并对其抗增殖活性进行了评估。结果表明，类似物20对PC-3细胞系的抗增殖活性比阳性对照CA-4更强。特别是，最有前景的化合物25在抑制HCT116细胞增殖方面比CA-4有5倍的改善，IC值为1.15 μM。进一步的流式细胞术分析表明，化合物20在PC-3细胞中对G/M期细胞周期阻滞有显著的剂量依赖性作用。从这项研究来看，类似物20和25是该结构类中最有效的抗癌剂，被认为是进一步开发抗癌药物的先导化合物。
