College of Life Sciences, Wuhan University, 299 Ba Yi Road, Wuchang, 430072, PR China.
School of Chemistry, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou, 510275, PR China.
Eur J Med Chem. 2019 Sep 15;178:154-167. doi: 10.1016/j.ejmech.2019.05.088. Epub 2019 Jun 2.
A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, 11s, 11v, 11x and 11y exhibited potent antiproliferative activity with IC value of lower than 10 μM against seven human tumor cell lines, and N-(3-methoxyphenyl)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent antiproliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an IC value of 2.56, 3.67, 3.46 and 2.71 μM, respectively. The antitumor efficacy of the representative compound 11x in mice was also evaluated, and the results showed that compound 11x effectively inhibited tumor growth and decreased tumor weight in animal models. Further investigation on mechanism of action indicated that compound 11x could inhibit colorectal cancer growth through ATG5-depenent autophagy pathway. Therefore, these quinoline derivatives are a new class of molecules that have the potential to be developed as new antitumor drugs.
设计、合成了一系列新型喹啉衍生物，并对其进行了抗增殖活性评价。结果表明，化合物 11p、11s、11v、11x 和 11y 对 7 个人类肿瘤细胞系表现出较强的抗增殖活性，IC 值低于 10μM，其中 N-(3-甲氧基苯基)-7-(3-苯基丙氧基)喹啉-4-胺 11x 对 HCT-116、RKO、A2780 和 Hela 细胞系的抑制活性最强，IC 值分别为 2.56、3.67、3.46 和 2.71μM。代表性化合物 11x 在小鼠中的抗肿瘤疗效也进行了评价，结果表明，化合物 11x 能有效抑制肿瘤生长，降低动物模型中的肿瘤重量。进一步的作用机制研究表明，化合物 11x 可通过 ATG5 依赖性自噬途径抑制结直肠癌细胞生长。因此，这些喹啉衍生物是一类具有开发成新型抗肿瘤药物潜力的新分子。
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