Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents
Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents
复制标题
作为潜在抗肿瘤药物的新型喹啉衍生物的设计、合成和生物学评价
DOI：
10.1016/j.ejmech.2019.05.088
复制
发表时间：
2019-09-15
影响因子：
6.7
通讯作者：
Cao, Rihui
中科院分区：
文献类型：
--
作者：
Su, Tong;Zhu, Jiongchang;Cao, Rihui
设计、合成了一系列新的喹啉衍生物，并对其抗肿瘤活性进行了评价。结果表明，化合物11 p、11 s、11 v、11 x和11 y显示出有效的抗增殖活性，其对7种人肿瘤细胞系的10（50）值低于10 μ M，而N-（3-甲氧基苯基）-7-发现（3-苯基丙氧基）喹啉-4-胺11 x是针对HCT-116，RKO，A2780和Hela细胞系，其10（50）值分别为2.56、3.67、3.46和2.71 μ M。还评价了代表性化合物11 x在小鼠中的抗肿瘤功效，结果显示化合物11 x在动物模型中有效抑制肿瘤生长并降低肿瘤重量。对作用机制的进一步研究表明，化合物11 x可以通过ATG 5依赖性自噬途径抑制结直肠癌生长。因此，这些喹啉衍生物是一类新的分子，有可能被开发为新的抗肿瘤药物。2019 Elsevier Masson SAS。All rights reserved.
A series of new quinoline derivatives was designed, synthesized and evaluated for their antiproliferative activity. The results demonstrated that compounds 11p, lls, 11v, llx and 11y exhibited potent anti proliferative activity with 10(50) value of lower than 10 mu M against seven human tumor cell lines, and N-(3methoxypheny1)-7- (3-phenylpropoxy)quinolin-4-amine 11x was found to be the most potent anti proliferative agent against HCT-116, RKO, A2780 and Hela cell lines with an 10(50) value of 2.56, 3.67, 3.46 and 2.71 mu M, 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 llx 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. 2019 Elsevier Masson SAS. All rights reserved.