Design and synthesis of some new 2,3′-bipyridine-5-carbonitriles as potential anti-inflammatory/antimicrobial agents

Abstract

Aim: Inflammation may cause accumulation of fluid in the injured area, which may promote bacterial growth. Other reports disclosed that non-steroidal anti-inflammatory drugs may enhance progression of bacterial infection. Results: This work describes synthesis of new series of 2,3′-bipyridine-5-carbonitriles as structural analogs of etoricoxib, linked at position-6 to variously substituted thio or oxo moieties. Biological screening results revealed that compounds 2b, 4b, 7e and 8 showed significant acute and chronic AI activities and broad spectrum of antimicrobial activity. In addition, similarity ensemble approach was applied to predict potential biological targets of the tested compounds. Then, pharmacophore modeling study was employed to determine the most important structural parameters controlling bioactivity. Moreover, title compounds showed physicochemical properties within those considered adequate for drug candidates. Conclusion: This study explored the potential of such series of compounds as structural leads for further modification to develop a new class of dual AI-antimicrobial agents.