Synthesis and biological evaluation of 2-(4-methylsulfonyl phenyl)indole derivatives: Multi-target compounds with dual antimicrobial and anti-inflammatory activities

Abstract

Three series of 2-(4-methylsulfonylphenyl) indole derivatives have been designed and synthesized. The synthesized compounds were evaluated for their antimicrobial, COX inhibitory and anti-inflammatory activities. Compound 7g was identified to be the most potent antibacterial candidate against strains of MRSA , E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii , respectively with safe therapeutic dose. Compounds 7a-k, 8a-c and 9a-c showed good anti-inflammatory activity with high selectivity toward COX-2 in comparison with reference drugs indomethacin and celecoxib. Compounds 9a-c were found to release moderate amounts of NO to decrease the side effects associated with selective COX-2 inhibitors. A molecular modeling study for compounds 7b, 7h, and 7i into COX-2 active site correlated with results of in vitro COX-2 inhibition assays.

Design, synthesis, biological assessment and in silico ADME prediction of new 2-(4-(methylsulfonyl) phenyl) benzimidazoles as selective cyclooxygenase-2 inhibitors

“…1,2 NSAIDs are still the rst choice for the management of such cases. 3 The inammatory process starts with the biotransformation of arachidonic acid (AA) in the cell membrane, and is then catalyzed by both cyclooxygenases (COXs) and lipoxygenase (LOX) enzyme families to produce prostaglandins (PGs) and leukotrienes (LTs), respectively. 4 NSAIDS are capable of reducing the production of key pro-inammatory mediator's prostaglandins (PGs) by the inhibition of constitutive (COX-1) and inducible (COX-2) isozymes.…”