Design, synthesis and biological evaluation of new quinoline derivatives as potential antitumor agents

摘要

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.