Synthesis of 2-Phenoxyacetic Acid Analogs for Evaluation of the Anti-inflammatory Potential and Subsequent  In Silico  Analysis

Md. Mofazzal Hossain; Bishyajit Kumar Biswas; Sukumar Bepary

doi:10.22146/ijc.96015

Synthesis of 2-Phenoxyacetic Acid Analogs for Evaluation of the Anti-inflammatory Potential and Subsequent In Silico Analysis

https://doi.org/10.22146/ijc.96015

Md. Mofazzal Hossain⁽¹⁾, Bishyajit Kumar Biswas⁽²⁾, Sukumar Bepary^(3*)

(1) Department of Pharmacy, Jagannath University, 9–10 Chittaranjan Avenue, Dhaka 1100, Bangladesh; Department of Pharmacy, University of Information Technology and Sciences, Holding 190, Road 5, Block J, Baridhara, Maddha Nayanagar, Vatara, Dhaka 1212, Bangladesh
(2) Department of Pharmacy, Jagannath University, 9–10 Chittaranjan Avenue, Dhaka 1100, Bangladesh
(3) Department of Pharmacy, Jagannath University, 9–10 Chittaranjan Avenue, Dhaka 1100, Bangladesh
(*) Corresponding Author

Abstract

Several 2-phenoxyacetic acid derivatives and their isosteres were synthesized in moderate to high yield (57–96%) for searching newer and safer alternatives to these existing anti-inflammatory agents. The compounds were characterized by ¹H-NMR, ¹³C-NMR and HRMS. The synthesized compounds have been subjected to in vitro anti-inflammatory activity using egg albumin denaturation and human red blood cell membrane stabilization methods. The compounds were also evaluated for their anti-inflammatory activity in the mice model. The synthesized compounds were subsequently subjected to docking analysis. The in vitro pharmacokinetic properties were analyzed by applying the pkCSM software and drug-likeness was checked by using Lipinski’s rule. Some synthesized esters and amides, like SM61, SM81, SM82, SM83, SM91 and SM101, were significantly more powerful as anti-inflammatory agents. The efficacies were correlated with their orientations in the binding pocket of the cyclooxygenase enzyme. The encouraging in vitro and in vivo activities, the optimum pharmacokinetic profile, and good drug-likeness indicated that these scaffolds could be considered for future discovery of newer nonsteroidal anti-inflammatory drugs (NSAIDs).

Keywords

writhing; HRBC; docking; pharmacokinetic profile

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DOI: https://doi.org/10.22146/ijc.96015