title: Synthesis of novel pyrazole–thiadiazole hybrid as potential potent and selective cyclooxygenase-2 (COX-2) inhibitors.
abstract: A series of 1,3,4-trisubstituted pyrazole derivatives (3 a-f), (4 a-f), and (5 a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 μM. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 μM), with a significant selectivity index (SI > 60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents.
authors.affiliation: Department of Pharmaceutical Chemistry, KLES College of pharmacy, KLE University, Nehrunagar, Belgaum 590 010, Karnataka, India. sgalegaon@klepharm.edu
authors.forename: S G
authors.initials: SG
authors.lastname: Alegaon
authors.forename: M B
authors.initials: MB
authors.lastname: Hirpara
authors.forename: K R
authors.initials: KR
authors.lastname: Alagawadi
authors.forename: K K
authors.initials: KK
authors.lastname: Hullatti
authors.forename: K
authors.initials: K
authors.lastname: Kashniyal
mesh_terms: D001665:Binding Sites; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000737:chemistry* / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011720:Pyrazoles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013830:Thiadiazoles; C031280:pyrazole; D051546:Cyclooxygenase 2