Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
Design, synthesis and biological evaluation of a series of pyrano chalcone derivatives containing indole moiety as novel anti-tubulin agents
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一系列含有吲哚部分的吡喃查尔酮衍生物作为新型抗微管蛋白药物的设计、合成和生物学评价
DOI：
10.1016/j.bmc.2014.02.028
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发表时间：
2014-04-01
影响因子：
3.5
通讯作者：
Chen, Lijuan
中科院分区：
文献类型：
--
作者：
Wang, Guangcheng;Li, Chunyan;Chen, Lijuan
合成了一系列新的含吲哚（3- 42,49a -49r）的吡查尔酮衍生物，并对其抗增殖活性进行了评价。在所有化合物中，化合物49b的左苯基环4位有一个丙酰氧基，右环上有一个n -甲基-5-吲哚，对包括多药耐药表型在内的所有被试癌细胞的细胞毒活性最强，其抑制癌细胞生长的IC50值在0.22 ~ 1.80 μ M之间，并且49b显著诱导细胞周期阻滞在G2/M期，抑制微管蛋白的聚合。分子对接分析证实49b在微管蛋白的秋水仙碱结合位点相互作用。在体内实验中，49b对BALB/c裸鼠HepG2人肝癌具有较强的抗肿瘤活性。这些结果表明，这些化合物是有希望的微管蛋白聚合抑制剂，具有潜在的治疗癌症的潜力。(C) 2014 Elsevier Ltd.版权所有。
A new series of pyrano chalcone derivatives containing indole moiety (3-42, 49a-49r) were synthesized and evaluated for their antiproliferative activities. Among all the compounds, compound 49b with a propionyloxy group at the 4-position of the left phenyl ring and N-methyl-5-indoly on the right ring displayed the most potent cytotoxic activity against all tested cancer cell lines including multidrug resistant phenotype, which inhibits cancer cell growth with IC50 values ranging from 0.22 to 1.80 mu M. Furthermore, 49b significantly induced cell cycle arrest in G2/M phase and inhibited the polymerization of tubulin. Molecular docking analysis demonstrated the interaction of 49b at the colchicine binding site of tubulin. In experiments in vivo, 49b exerted potent anticancer activity in HepG2 human liver carcinoma in BALB/c nude mice. These results indicated these compounds are promising inhibitors of tubulin polymerization for the potential treatment of cancer. (C) 2014 Elsevier Ltd. All rights reserved.