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)

  • Bioorg Chem. 2020 Oct;103:104189. doi: 10.1016/j.bioorg.2020.104189.
Xin-Yang Li  1 ,  Shuai Li  2 ,  Guo-Qing Lu  2 ,  De-Pu Wang  2 ,  Kai-Li Liu  2 ,  Xin-Hua Qian  2 ,  Wen-Han Xue  2 ,  Fan-Hao Meng  3
Affiliations
  • 1. School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China; Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang 110122, China.
  • 2. School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China.
  • 3. School of Pharmacy, China Medical University, 77 Puhe Road, North New Area, Shenyang 110122, China. Electronic address: [email protected].
PMID: 32890996 DOI: 10.1016/j.bioorg.2020.104189
Abstract

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.

Keywords
Antitumor; Apoptosis; Multiple myeloma (MM).
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