Chemistry of Natural and Microbial Products Department, Pharmaceutical and Drug Industries Research Division, National Research Centre, El-Bohouth Street, 12622 Dokki, Cairo, Egypt.
Eur J Med Chem. 2012 Jan;47(1):387-98. doi: 10.1016/j.ejmech.2011.11.007. Epub 2011 Nov 11.
The starting material, 4-(1-indol-2-yl)phenol 1 was obtained via Fischer synthesis. Vilsmeir Haack(')s formylation of 1 gave the carboxaldehyde derivative 2 which was subjected to different reactions affording the 3-substituted compounds 3-10. Compound 1 reacted with halo esters to give 11 and 12a,b. The reaction of 12a with various amino derivatives gave compounds 13-16. The hydrazide derivative 15a reacted with 1,3-diketones, ethyl acetoacetate and aromatic carboxylic acid derivatives to give 17a,b, 18 and 19a-e, respectively. Antitumor activity of target compounds were tested against breast cancer cell lines (MCF-7) and (MDA-MB-231). The most potent compound was 3e with IC(50) = 1.60 nM against (MCF-7). Docking was performed on colchicine binding site of tubulin to study the binding mode of the designed compounds.
起始原料 4-(1-吲哚-2-基)苯酚 1 通过费歇尔合成法得到。Vilsmeir Haack（'）对 1 的甲酰化得到了醛衍生物 2，该醛衍生物经过不同的反应得到了 3-取代的化合物 3-10。化合物 1 与卤代酯反应得到了 11 和 12a,b。12a 与各种氨基衍生物的反应得到了化合物 13-16。酰肼衍生物 15a 与 1,3-二酮、乙酰乙酸乙酯和芳香羧酸衍生物反应得到了 17a,b、18 和 19a-e。对目标化合物进行了针对乳腺癌细胞系 (MCF-7) 和 (MDA-MB-231) 的抗肿瘤活性测试。最有效的化合物是 3e，对 (MCF-7) 的 IC(50) 为 1.60 nM。对接是在微管蛋白的秋水仙碱结合位点上进行的，以研究设计化合物的结合模式。
