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

A series of novel β-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 IC 50 values of 2.71, 2.02, and 3.86 μM, respectively. The antitumor efficiency of compound 6g in 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. A series of novel β-carbolines was synthesized and evaluated as potential antitumor agents. Compound 6g effectively inhibited tumor growth in BALB/c mice by triggering an autophagy pathway dependent on ATG5/ATG7. [Display omitted] • A series of novel β-carbolines was prepared and evaluated as potential antitumor agents. • Compound 6g was found to be the most potent antitumor agent in vitro. • Compound 6g significantly suppressed tumor development and reduced tumor weight in animal model. • Compound 6g inhibited HCT116 growth by stimulating the ATG5/ATG7-dependent autophagic pathway. [ABSTRACT FROM AUTHOR]