2. Academic Validation
  3. Synthesis and antiproliferative evaluation of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives

Synthesis and antiproliferative evaluation of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives

  • Bioorg Med Chem. 2011 Dec 15;19(24):7653-63. doi: 10.1016/j.bmc.2011.10.014.
Chih-Hua Tseng 1,  Cherng-Chyi Tzeng,  Kuin-Yu Chung,  Chai-Lin Kao,  Chih-Yao Hsu,  Chih-Mei Cheng,  Keng-Shiang Huang,  Yeh-Long Chen
Affiliations

Affiliation

  • 1 Department of Medicinal and Applied Chemistry, College of Life Science, and Center of Excellence for Environmental Medicine, Kaohsiung Medical University, Kaohsiung City 807, Taiwan.
PMID: 22079254 DOI: 10.1016/j.bmc.2011.10.014
Abstract

A number of 6-aryl-11-iminoindeno[1,2-c]quinoline derivatives were synthesized and evaluated for their antiproliferative activities. Among them, (E)-6-{4-[3-(dimethylamino)propoxy]phenyl}-2-fluoro-9-hydroxy-11H-indeno[1,2-c]quinolin-11-one O-3-(dimethylamino)propyl oxime (23a) was the most active, exhibited GI(50) values of 0.64, 0.39, 0.55, 0.67, and 0.65μM against the growth of Hep G2, Hep 3B, A549, H1299, and MDA-MB-231, respectively. Compound 23a inhibited the growth of hepatoma cell lines in a dose- and time-dependent manner. The proportion of cells was decreased in the G1 and accumulated in G2/M phase after 12h treatment of 23a, while the hypodiploid (sub-G0/G1 phase) cells increased. Further investigations have shown that 23a induced cell cycle arrest at G2/M phase and induce Apoptosis via activation of p53, Bax, and Caspase-8 which consequently cause cell death.

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