title: 1,3,4-Trisubstituted pyrazole analogues as promising anti-inflammatory agents.
abstract: Twenty-two 1,3,4-trisubstituted pyrazole (3a-d), (4a-d), (5a-d), (6a-l) derivatives were synthesized and structure of newly synthesized compounds were characterized by IR, (1)H NMR, (13)C NMR, and mass spectral analysis. These compounds were screened for the anti-inflammatory activity by carrageenan-induced paw edema method. Compounds 5a, and 5b showed excellent anti-inflammatory activity (⩾84.2% inhibition) and 3a, 3b, and 3c showed good anti-inflammatory activity (⩾64.6% inhibition) compared to that of the standard drug diclofenac (86.72%) when measured 3h after the carrageenan injection. Moreover, the cyclooxygenase (COX) enzyme inhibitor activity of selected compounds, which are the excellent anti-inflammatory activities in carrageenan-induced paw edema model, was investigated in vitro COX inhibition assay. Molecular docking study further helped in supporting the observed activity. In addition compound 5a exhibited considerable cytotoxic activity against MCF-7 cell line with IC50 value 6.5 μM.
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Nehrunagar, Belgaum 590 010, Karnataka, India. Electronic address: sgalegaon@klepharm.edu.
authors.forename: S G
authors.initials: SG
authors.lastname: Alegaon
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Nehrunagar, Belgaum 590 010, Karnataka, India.
authors.forename: K R
authors.initials: KR
authors.lastname: Alagawadi
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Nehrunagar, Belgaum 590 010, Karnataka, India.
authors.forename: M K
authors.initials: MK
authors.lastname: Garg
authors.affiliation: Regional Medical Research Centre (ICMR), Nehrunagar, Belgaum, Karnataka, India.
authors.forename: K
authors.initials: K
authors.lastname: Dushyant
authors.affiliation: Department of Pharmaceutical Chemistry, College of Pharmacy, Madras Medical College, Chennai 03, India.
authors.forename: D
authors.initials: D
authors.lastname: Vinod
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002351:Carrageenan / Q000008:administration & dosage; D049109:Cell Proliferation / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D012756:Sheep; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: 1,3,4-Thiadiazole; Anti-inflammatory activity; COX-1 and COX-2; Molecular docking; Pyrazole; Thiazole; Thiazolidinone