title: Novel 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene analogues as selective COX-2 inhibitors: Design, synthesis, anti-inflammatory evaluation, and molecular docking studies.
abstract: A series of 2-phenyl-4,5,6,7-tetrahydro[b]benzothiophene derivatives were synthesized and evaluated for in vitro COX inhibitory potential. Within the series, compounds 4a, 4j, 4k, and 4q were identified as potential and selective COX-2 inhibitors with COX-2 IC50in 0.31-1.40µM range; COX-2 selectivity index (SI)=48.8-183.8 range and they showed percent PGE-2 inhibitory activity in the range of 25.4-46.9. Further, compounds 4a, 4j, 4k and 4q displayed potent anti-inflammatory activity with percentage rise in paw volume ranging from 21.1-30.5 at 180min, while celecoxib demonstrated 19.6 percentage rise at the same dose at 180min in carrageenan-induced rat paw edema assay. Cell viability via MTT assay showed no cytotoxicity up to 80µM concentrations. Molecular docking study of potent compounds in the series showed Gscore comparable to celecoxib with similar binding orientation for the COX-2 active site which also corroborates the observed in vitro COX-2 inhibition.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India.
authors.forename: Chetan K
authors.initials: CK
authors.lastname: Khatri
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India.
authors.forename: Krishna S
authors.initials: KS
authors.lastname: Indalkar
authors.affiliation: Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dist-Dhule 425405, Maharashtra, India.
authors.forename: Chandragouda R
authors.initials: CR
authors.lastname: Patil
authors.affiliation: Department of Pharmacology, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, Dist-Dhule 425405, Maharashtra, India.
authors.forename: Sameer N
authors.initials: SN
authors.lastname: Goyal
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, Mumbai 400019, Maharashtra, India. Electronic address: gu.chaturbhuj@gmail.com.
authors.forename: Ganesh U
authors.initials: GU
authors.lastname: Chaturbhuj
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002351:Carrageenan; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D004487:Edema / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D062105:Molecular Docking Simulation; D000067996:RAW 264.7 Cells; D051381:Rats; D013876:Thiophenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D013876:Thiophenes; C088015:benzothiophene; D002351:Carrageenan
keywords: 4,5,6,7-Tetrahydro[b]benzothiophene; Anti-inflammatory activity; COX-2 selective; Carrageenan-induced rat paw edema; Molecular docking