title: Design, synthesis, cyclooxygenase inhibition and biological evaluation of new 1,3,5-triaryl-4,5-dihydro-1H-pyrazole derivatives possessing amino/methanesulfonyl pharmacophore.
abstract: A new series of 1,3,5-triaryl-4,5-dihydro-1H-pyrazole 10a-l was designed and synthesized via cyclization of chalcones 8a-f with 4-amino/methanesulfonylphenylhydrazine hydrochloride 9a-b. All the synthesized compounds were evaluated for their cyclooxygenase (COX) inhibition, anti-inflammatory activity, ulcerogenic liability and analgesic activity. All compounds were more COX-2 inhibitors than COX-1. While most compounds showed good anti-inflammatory activity, the trimethoxy derivatives (10a, 10b, 10g and 10h) were the most potent derivatives (ED50=55.78, 53.99, 67.65 and 69.20μmol/kg respectively) in comparison with celecoxib (ED50=82.15μmol/kg). Compounds 10a, 10b, 10g and 10h (ulcer index=2.68, 1.20, 2.63 and 2.66 respectively) showed less ulceration effect than celecoxib (ulcer index=2.90). Also, Compounds 10a, 10b, 10g and 10h showed analgesic activity higher than celecoxib and comparable to that of ibuprofen. In addition, molecular docking studies were performed for compounds 10a, 10b, 10g and 10h and the results were in agreement with that obtained from the in vitro COX inhibition assays.
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef 62514, Egypt. Electronic address: khaled.ahmed@pharm.bsu.edu.eg.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Beni-Suef University, Beni-Suef 62514, Egypt.
authors.forename: Wael A A
authors.initials: WA
authors.lastname: Fadaly
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008698:Mesylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D017208:Rats, Wistar; D012756:Sheep
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D008698:Mesylates; D011720:Pyrazoles; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: 1,3,5-Triaryl-4,5-dihydro-1H-pyrazole; Anti-inflammatory; Cyclooxygenase-2 inhibitors