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

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Abstract

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.

Original languageEnglish
Pages (from-to)2541-2551
Number of pages11
JournalMolecular BioSystems
Volume12
Issue number8
DOIs
Publication statusPublished - 2016 Jan 1

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Biology

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