title: Efficacy of phenyl quinoline phenol derivatives as COX-2 inhibitors; an approach to emergent the small molecules as the anti-inflammatory and analgesic therapeutics.
abstract: 2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) with COX-2 enzyme inhibition, analgesic, anti-inflammatory and antipyretic potentials were executed and reported. From the in vitro COX-2 enzyme inhibition assay, compounds 4 h (IC500.026 µM) and 4j (IC500.102 µM) were found as most potent COX-2 inhibitors. Consequently, to get more insight into the binding mode with COX-2, compounds 4a-l were docked into the COX-2 (PDB ID: 1CX2) active site. In the Human Red Blood Cells (HRBC) membrane stabilization assay (in vitro anti-inflammatory), compounds 4f (IC500.064 µM) substituted with -OH (R1) and -3Cl (R2), 4 h (IC500.021 µM), 4i (IC500.484 µg/ml) and 4j (IC500.092 µM) with -CHO containing alkanol and ether group at R1 and -4F, -4Br and -OMe at R2 (C2) were showed most potent anti-inflammatory activity. Eventually, acute toxicity studies revealed that 2-(4-phenylquinoline-2-yl)phenol derivatives (4a-l) are safe up to a toleration dose limit of 100 µg/kg body weight. In the Backer's yeast intraperitoneal injection test, compounds 4f, 4 h and 4j produced significant (p < 0.05) antipyretic activity at 1, 1.5, 2 and 2.5 h, whereas test compound 4j and the reference drug indomethacin showed significant antipyretic activity throughout the observation period up to 2.5 h. Promising in vivo results obtained were correlated with the standard non-steroidal anti-inflammatory drugs and the compounds 4f, 4 h, 4i, 4j, and 4 l were efficiently identified as therapeutically potent/fortune moieties as non-steroidal anti-inflammatory agents/analgesics. At the end, ulcerogenic study result ensured that the tested 2-(4-phenylquinoline-2-yl)phenol derivatives created no side-effect.
authors.affiliation: School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, 632014, India.
authors.forename: A
authors.identifier: http://orcid.org/0000-0002-7065-5884
authors.initials: A
authors.lastname: Manikandan
authors.affiliation: Center of Advanced Study in Marine Biology, Annamalai University, Parangipettai, 608 502, India.
authors.forename: S
authors.initials: S
authors.lastname: Ravichandran
authors.affiliation: School Advanced Sciences, VIT University, Vellore, Tamil Nadu, 632014, India.
authors.forename: K I
authors.initials: KI
authors.lastname: Sathiyanarayanan
authors.affiliation: School of Bio-Science and Technology, VIT University, Vellore, Tamil Nadu, 632014, India. siva_kumar.a@vit.ac.in.
authors.forename: A
authors.initials: A
authors.lastname: Sivakumar
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D010636:Phenols; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D054852:Small Molecule Libraries / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D052246:Cyclooxygenase 2 Inhibitors; D010636:Phenols; D011804:Quinolines; D054852:Small Molecule Libraries; D002351:Carrageenan; D051546:Cyclooxygenase 2
keywords: Analgesics; Anti-inflammatory; COX-2; Cytotoxicity; IC50; Molecular docking; NSAIAs