Discovery of novel 4(1H)-quinolone derivatives as potential antiproliferative and apoptosis inducing agents

  • Bioorg Med Chem Lett. 2017 Sep 1;27(17):4185-4189. doi: 10.1016/j.bmcl.2017.07.005.
Ping Zhou  1 ,  Linsheng Huang  1 ,  Jie Zhou  2 ,  Bin Jiang  1 ,  Yanmei Zhao  1 ,  Xuehua Deng  2 ,  Qin Zhao  2 ,  Fei Li  3
Affiliations
  • 1. Department of Hepatopancreatobiliary Surgery, Taihe Hospital, Hubei University of Medicine, Hubei, China.
  • 2. School of Pharmaceutical Sciences, Hubei University of Medicine, Hubei, China.
  • 3. School of Pharmaceutical Sciences, Hubei University of Medicine, Hubei, China. Electronic address: [email protected].
PMID: 28757067 DOI: 10.1016/j.bmcl.2017.07.005
Abstract

A series of novel 4(1H)-quinolone derivatives was synthesized and evaluated for antiproliferative activity in vitro. The results showed that these compounds exhibited more potent antiproliferative effect against a panel of human tumorcelllines than the lead compound 7-chloro-4(1H)-quinolone 1. Compound 7e was found to be the most potent antiproliferative agent and to exhibit selective cytotoxic activity against HepG2 cell lines with IC50 value lower than 1.0μM. Annexin V/FITC-PI assay showed that compound 7e induced Apoptosis in HepG2 cells with a dose-dependent manner. Western blotting analysis indicated that compound 7e induced cell cycle arrest in G2/M phase by p53-depedent pathway.

Keywords
Antiproliferative activity; Apoptosis; Quinolone; Synthesis.