Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents

  • Bioorg Med Chem Lett. 2014 May 15;24(10):2324-8. doi: 10.1016/j.bmcl.2014.03.072.
Ji-Wen Yuan  1 ,  She-Feng Wang  1 ,  Zhong-Liang Luo  1 ,  Han-Yue Qiu  1 ,  Peng-Fei Wang  1 ,  Xin Zhang  1 ,  Yong-An Yang  1 ,  Yong Yin  1 ,  Fei Zhang  1 ,  Hai-Liang Zhu  2
Affiliations
  • 1. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
  • 2. State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China. Electronic address: [email protected].
PMID: 24731281 DOI: 10.1016/j.bmcl.2014.03.072
Abstract

A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a-7a, 1b-7b, 1c-7c, 1d-7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC50=0.86μM for Hela and IC50=0.12μM for EGFR). Structure-activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (-OCH3>-CH3>-H>-Br>-Cl>-F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p-π bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent.

Keywords
Anti-tumor activity; Cell migration; EGFR inhibitors; Structure–activity relationship.