Efficacy of phenyl quinoline phenol derivatives as COX-2 inhibitors; an approach to emergent the small molecules as the anti-inflammatory and analgesic therapeutics

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 (IC50 0.026 A mu M) and 4j (IC50 0.102 A mu M) 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 (IC50 0.064 A mu M) substituted with -OH (R-1) and -3Cl (R-2), 4 h (IC50 0.021 A mu M), 4i (IC50 0.484 A mu g/ml) and 4j (IC50 0.092 A mu M) 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 A mu g/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.