2. Academic Validation
  3. Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents

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

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: zhuhl@nju.edu.cn.
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.

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