Background: Quinolines have been characterized as a class of potential antitumor agents,
and a large number of natural and synthetic quinolines acting as antitumor agents were reported.
Methods: A series of 7-chloro-4(1H)-quinolone derivatives were synthesized. The antiproliferative
effect of these compounds was evaluated by MTT assay against five human tumor cell lines. The
mechanism of action of the selected compound 7h was also investigated.
Results and Discussion: Most of the compounds had more potent antiproliferative activities than
the lead compound 7-chloro-4(1H)-quinolone 6b. Compound 7h was found to be the most potent
antiproliferative agent against human tumor cell lines. Further investigation demonstrated that compound
7h triggered ATG5-dependent autophagy of colorectal cancer cells by promoting the functions
of LC3 proteins.
Conclusion: These results were useful for designing and discovering more potent novel antitumor
agents endowed with better pharmacological profiles.