title: 3-methyl-2-phenyl-1-substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents.
abstract: In a new group of 3-methyl-2-phenyl-1-substituted-indole derivatives (10a-f), the indomethacin analogs were prepared via the Fisher indole synthesis reaction of propiophenone with appropriately substituted phenylhydrazine hydrochloride. This is followed by the insertion of the appropriate benzyl or benzoyl fragment. All the synthesized compounds were evaluated for their anti-inflammatory (in vitro and in vivo) and analgesic activities. The methanesulphonyl derivatives 10d, e and f showed the highest anti-inflammatory (in vitro and in vivo) and analgesic activities. In addition, molecular docking studies were performed on compounds 10a-f and the results were in agreement with that obtained from the in vitro COX inhibition assays. The significant anti-inflammatory and analgesic activities exhibited by 10d and 10e warrant continued preclinical development as potential anti-inflammatory and analgesic agents.
authors: a Department of Pharmaceutical Organic Chemistry and.
authors: Khaled R A
authors: KR
authors: Abdellatif
authors: a Department of Pharmaceutical Organic Chemistry and.
authors: Phoebe F
authors: PF
authors: Lamie
authors: b Department of Pharmacology , Faculty of Pharmacy, Beni-Suef University , Beni-Suef , Egypt , and.|c Department of Pharmacology , Sharjah Institute for Medical Research, College of Pharmacy, University of Sharjah , Sharjah , UAE.
authors: Hany A
authors: HA
authors: Omar
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D020134:Catalytic Domain; D060326:Chemistry Techniques, Synthetic; D051545:Cyclooxygenase 1 / Q000737:chemistry / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D007211:Indoles / Q000737:chemistry*; D007213:Indomethacin / Q000031:analogs & derivatives; D020128:Inhibitory Concentration 50; D051379:Mice; D062105:Molecular Docking Simulation; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007211:Indoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D007213:Indomethacin
keywords: Anti-inflammatory activity; cyclooxygenase; indomethacin; molecular modeling