Synthesis and in vitro and in vivo evaluation of novel bivalent quinolines as antitumor agents via targeting autophagy in cervical cancer

A series of novel bivalent quinolines with a spacer of four to six methylene units between the phenoxy group in the position-7 and various substituents in the position-4 of quinoline skeleton, respectively, were synthesized and evaluated as anticancer agents. The data showed that the majority of the compounds had significant antiproliferative activity with IC₅₀ values less than 50 μM against human cancer cell lines. Among them, compound 4b exhibited the strongest antiproliferative activity against HCT116, A549, BGC823, HeLa and MCF-7 cell lines with an IC₅₀ values of 0.26, 2.75, 4.06, 3.71 and 3.08 μM, respectively. Further studies on the anticancer effects in mice of compound 4b showed its capacity to inhibit tumor growth and markedly reduce tumor size of cervical cancer. Moreover investigation on the underlying mechanism of action indicated that compound 4b didn't trigger apoptotic processes in cervical cancer cell lines, but inhibit cervical cancer growth through inducing autophagy via the ATG5/ATG7 pathway.