Novel series of phenylalanine analogs endowed with promising anti-inflammatory activity: Synthesis, pharmacological evaluation, and computational insights
Medicinal Chemistry Research
Department of Pharmaceutical Chemistry, K.L.E. University College of Pharmacy, Vidyanagar, Hubli, Karnataka, India; Department of Pharmaceutical Chemistry, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban, South Africa; Department of Pharmacology, K.L.E. University College of Pharmacy, Vidyanagar, Hubli, Karnataka, India
Abstract A novel series of methyl-2-(substituted benzylideneamino)-3-phenyl propionate (2a-j) derivatives have been synthesized. The title compounds (2a-j) were screened for in vivo acute anti-inflammatory and analgesic activities at a dose of 200 mg/kg b.w. Compound 2e exhibited the most promising and significant anti-inflammatory profile while compounds 2b, 2h, 2i, and 2j showed moderate to good inhibitory activity at 2nd and 4th h, respectively. These compounds were also found to have considerable analgesic activity (acetic acid-induced writhing model) and antipyretic activity (yeast-induced pyrexia model). In addition, the tested compounds were also found to possess less degree of ulcerogenic potential as compared to the standard NSAIDs. The synthesized compounds were further evaluated for their inhibitory activity against cyclooxygenase enzyme (COX-1/COX-2), by in vitro colorimetric COX (ovine) inhibitor screening assay method. The results revealed that the compounds 2b, 2e, 2h, 2i, and 2j exhibited selective and effective inhibition against COX-2. In an attempt to understand the ligand-protein interactions in terms of their binding affinity, docking studies were also performed using Molegro Virtual Docker (MVD-2013, 6.0) for the title compounds. It was observed that the binding affinities calculated were in agreement with the experimental IC<inf>50</inf> values. Graphical Abstract: [Figure not available: see fulltext.] © 2014 Springer Science+Business Media New York.