作为康普他汀A-4类似物的1,2-二芳基吡咯的合成及生物学评价
Synthesis and Biological Evaluations of 1,2-Diaryl Pyrroles as Analogues of Combretastatin A-4.
作者信息
Sun Jun, Chen Lei, Liu Chunjiang, Wang Zhan, Zuo Daiying, Pan Jiatong, Qi Huan, Bao Kai, Wu Yingliang, Zhang Weige
机构信息
Clinical Pharmacology Laboratory, Henan Province People's Hospital, Zhengzhou University People's Hospital, 7 Weiwu Road, Jinshui District, Zhengzhou, 450003, China.
Key Laboratory of Structure-Based Drug Design and Discovery, Ministry of Education, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, 110016, China.
出版信息
Chem Biol Drug Des. 2015 Dec;86(6):1541-7. doi: 10.1111/cbdd.12617. Epub 2015 Sep 25.
A series of novel 1,2-diaryl pyrroles as analogues of combretastatin A-4 (CA-4, 1a) were synthesized and evaluated for their antitumour potential against three cancer cell lines. Most compounds exhibited growth inhibition against all of the cancer cell lines. Compound 7q not only exhibited prominent antitumour efficacy with IC50 values of 0.390 μm in SGC-7901, 0.070 μm in HT-1080 and 0.045 μm in KB cell lines but also showed low activity with IC50 values of 30.08 μm in normal L929 cell line. Moreover, compound 7q inhibited tubulin polymerization into microtubules and caused microtubule destabilization. A molecular docking study of 7q was performed to determine its binding mode at the colchicine site in the tubulin dimer.
合成了一系列作为康普瑞他汀A-4（CA-4，1a）类似物的新型1,2-二芳基吡咯，并评估了它们对三种癌细胞系的抗肿瘤潜力。大多数化合物对所有癌细胞系均表现出生长抑制作用。化合物7q不仅在SGC-7901细胞系中表现出显著的抗肿瘤功效，IC50值为0.390μm，在HT-1080细胞系中为0.070μm，在KB细胞系中为0.045μm，而且在正常L929细胞系中表现出低活性，IC50值为30.08μm。此外，化合物7q抑制微管蛋白聚合成微管并导致微管不稳定。对7q进行了分子对接研究，以确定其在微管蛋白二聚体中秋水仙碱位点的结合模式。
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