Design, synthesis and pharmacological evaluation of ß-carboline derivatives as potential antitumor agent via targeting autophagy.

ABSTRACT

A series of novel ß-carboline derivatives was designed, synthesized and evaluated as potential anticancer agents. Among them, compound 6g showed the most potent antiproliferative activity against the 786-0, HT-29 and 22RV1 cell lines with IC50 values of 2.71, 2.02, and 3.86 µM, respectively. The antitumor efficiency of compound 6gin vivo was also evaluated, and the results revealed that compound 6g significantly suppressed tumor development and reduced tumor weight in a mouse colorectal cancer homograft model. Further investigation on mechanisms of action demonstrated that compound 6g inhibited HCT116 cell growth by stimulating the ATG5/ATG7-dependent autophagic pathway. These molecules might be served as candidates for further development of colorectal cancer therapy agent.