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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 - Jan 1 2016

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Cyclooxygenase 2 Inhibitors
Anti-Inflammatory Agents
Molecular Docking Simulation
Non-Steroidal Anti-Inflammatory Agents
Prostaglandin-Endoperoxide Synthases
Human Body
Antineoplastic Agents
Prostaglandins
Catalytic Domain
Pharmacology
In Vitro Techniques
Enzymes
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology

Cite this

Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations. / Tseng, Tien Sheng; Chuang, Show Mei; Hsiao, Nai Wan; Chen, Yi Wen; Lee, Yu Ching; Lin, Chi Chen; Huang, Cheng; Tsai, Keng Chang.

In: Molecular BioSystems, Vol. 12, No. 8, 01.01.2016, p. 2541-2551.

Research output: Contribution to journalArticle

Tseng, Tien Sheng ; Chuang, Show Mei ; Hsiao, Nai Wan ; Chen, Yi Wen ; Lee, Yu Ching ; Lin, Chi Chen ; Huang, Cheng ; Tsai, Keng Chang. / Discovery of a potent cyclooxygenase-2 inhibitor, S4, through docking-based pharmacophore screening, in vivo and in vitro estimations. In: Molecular BioSystems. 2016 ; Vol. 12, No. 8. pp. 2541-2551.
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AU - Hsiao, Nai Wan

AU - Chen, Yi Wen

AU - Lee, Yu Ching

AU - Lin, Chi Chen

AU - Huang, Cheng

AU - Tsai, Keng Chang

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