Synthesis, cyclooxygenase inhibition, anti-inflammatory evaluation and gastric liability of some novel indole derivatives as a selective COX-2 inhibitors

Research Abstract

A new group of (4-substitutedphenyl)(3-((2-(4- substitutedphenyl)hydrazono)methyl)-1H-indol-1-yl)methanone derivatives 13a-f as indomethacin analogs was synthesized through N-benzoylation of indole-3-cabaldehyde with the appropriate benzoyl fragment followed by reaction with substituted phenylhydrazine. All the synthesized compounds were evaluated in vitro for COX-1/COX-2 inhibitory activity and in vivo for their anti-inflammatory activity in comparison with the parent drug indomethacin. Compounds 13a,b,d,e which contain SO2Me or SO2NH2 group as a pharmacophore of COX-2, exhibited the most anti-inflammatory and selectivity activies so, they were more evaluated by calculating their ED50% doses and ulcerogenic indices to ensure their gastric safety margin relative to indomethacin.

Research Keywords

NSAIDS; Cyclooxygenase; Indomethacin; Anti-inflammatory activity; Ulcerogenicity