Structure-activity relationship of celecoxib and rofecoxib for the membrane permeabilizing activity

Naoki Yamakawa, Koichiro Suzuki, Yasunobu Yamashita, Takashi Katsu, Kengo Hanaya, Mitsuru Shoji, Takeshi Sugai, Tohru Mizushima

研究成果: Article査読

12 被引用数 (Scopus)

抄録

Non-steroidal anti-inflammatory drugs (NSAIDs) achieve their anti-inflammatory effect by inhibiting cyclooxygenase activity. We previously suggested that in addition to cyclooxygenase-inhibition at the gastric mucosa, NSAID-induced gastric mucosal cell death is required for the formation of NSAID-induced gastric lesions in vivo. We showed that celecoxib exhibited the most potent membrane permeabilizing activity among the NSAIDs tested. In contrast, we have found that the NSAID rofecoxib has very weak membrane permeabilizing activity. To understand the membrane permeabilizing activity of coxibs in terms of their structure-activity relationship, we separated the structures of celecoxib and rofecoxib into three parts, synthesized hybrid compounds by substitution of each of the parts, and examined the membrane permeabilizing activities of these hybrids. The results suggest that the sulfonamidophenyl subgroup of celecoxib or the methanesulfonylphenyl subgroup of rofecoxib is important for their potent or weak membrane permeabilizing activity, respectively. These findings provide important information for design and synthesis of new coxibs with lower membrane permeabilizing activity.

本文言語English
ページ(範囲)2529-2534
ページ数6
ジャーナルBioorganic and Medicinal Chemistry
22
8
DOI
出版ステータスPublished - 2014 4 15

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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