Design, synthesis and biological evaluation of novel (E)-N-phenyl-4-(pyridine-acylhydrazone) benzamide derivatives as potential antitumor agents for the treatment of multiple myeloma (MM)

A series of novel (E)-N-phenyl-4-(pyridine-acylhydrazone) benzamide derivatives were designed, synthesized, and evaluated for their anti-proliferative activity against two different human Cancer cell lines and one human normal cell line. Compound 8b had the best anti-proliferative activity (IC₅₀ = 0.12 ± 0.09 μM, RPMI8226 cells) than the other compounds. And compound 8b had lower toxicity than imatinib. Flow cytometry analysis showed that compound 8b could arrest the cell cycle at the G0/G1 phase, and induce Apoptosis of RPMI8226 cells by promoting mitochondrial ROS release, thereby effectively inhibiting cell proliferation. Our findings provided a promising lead compound 8b for further structural optimization and will be instructive for the discovery of more potent antitumor drugs with high selectivity and low toxicity.