Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations

Tien Sheng Tseng, Show Mei Chuang, Nai Wan Hsiao, Yi Wen Chen, Yu Ching Lee, Chi Chen Lin, Cheng Huang, Keng Chang Tsai

研究成果: 雜誌貢獻文章同行評審

3 引文 斯高帕斯(Scopus)

摘要

Cyclooxygenase (COX; EC: 1.14.99.1), the key enzyme in prostaglandin production in the human body, is a major pharmacological target for developing anti-inflammatory agents. Nonsteroidal anti-inflammatory drugs exhibit anti-inflammatory and analgesic activities when inhibiting COX-2 but cause gastrointestinal toxicity and other side effects because of concurrent inhibition of COX-1. Thus, potent and safe inhibitors against COX-2 are urgently required. We constructed a novel docking-based pharmacophore model for screening selective COX-2 inhibitors and discovered compounds S1, S2, S3, and S4, which apparently inhibit COX-2. Particularly, S4 inhibits COX-2 in vitro and shows a potent anti-inflammatory effect in vivo without cytotoxicity. Molecular docking analyses revealed that S4 interacted satisfactorily with the active site of COX-2 but not with that of COX-1. This reveals that S4 more specifically inhibits COX-2 and has potential for application in developing anti-inflammatory and anticancer agents.
原文英語
頁(從 - 到)2541-2551
頁數11
期刊Molecular BioSystems
12
發行號8
DOIs
出版狀態已發佈 - 一月 1 2016

ASJC Scopus subject areas

  • 生物技術
  • 分子生物學

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