Synthesis, in vitro, and in vivo biological evaluation and molecular docking simulations of chiral alcohol and ether derivatives of the 1,5-diarylpyrrole scaffold as novel anti-inflammatory and analge
详细信息 查看全文
- 作者：Mariangela Biava ; Giulio C. Porretta ; Giovanna Poce ; Sibilla Supino ; Fabrizio Manetti ; Stefano Forli ; Maurizio Botta ; Lidia Sautebin ; Antonietta Rossi ; Carlo Pergola ; Carla Ghelardini ; Monica Norcini
- 关键词：Anti-inflammatory ; NSAIDs ; Analgesic agents ; COX-1 inhibitors ; COX-2 inhibitors ; Coxibs ; Celecoxib
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2008
- 出版时间：1 September 2008
- 年：2008
- 卷：16
- 期：17
- 页码：8072-8081
- 全文大小：1418 K
文摘
Following our previous research on anti-inflammatory drugs (NSAIDs), we report here the synthesis of chiral 1,5-diarylpyrroles derivatives that were characterized for their in vitro inhibitory effects toward cyclooxygenase (COX) isozymes. Analysis of enzymatic affinity and COX-2 selectivity led us to the selection of one compound (+/−)-10b that was further tested in vitro in the human whole blood (HWB) and in vivo for its anti-inflammatory activity in mice. The affinity data have been rationalized through docking simulations.