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 IC50 values.
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Acknowledgments
The authors express their sincere thanks to The Principal, KLEU’s College of Pharmacy, Hubli (India), and The College of Health Sciences, University of KwaZulu-Natal (UKZN, South Africa) for providing necessary facilities and funding to carry out this work. Authors also express special thanks to Sapco Laboratories Pvt. Ltd., Chennai (Tamilnadu, India) for providing gift samples of NSAIDs. We sincerely express our gratitude to Dr.L.V.G.Nargund, Director, Nargund College of Pharmacy, Bangalore (India) for his scientific encouragement. Authors are grateful to NMR centre, School of Chemistry and Physics, UKZN (South Africa) for NMR spectral data. We express our gratitude to The Director, SAIF, Punjab University (India) for elemental analysis and sincerely thank Dr. Rene Thomsen for providing MVD-2013 (version: 6.0) trial license.
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Palkar, M.B., Praveen, D.M., Ronad, P.M. et al. Novel series of phenylalanine analogs endowed with promising anti-inflammatory activity: synthesis, pharmacological evaluation, and computational insights. Med Chem Res 24, 1988–2004 (2015). https://doi.org/10.1007/s00044-014-1272-x
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DOI: https://doi.org/10.1007/s00044-014-1272-x