Synthesis of novel triazole functionalized pyridine derivatives as potential antimicrobial and anti-biofilm agents

Abstract

A series of novel 1-substituted (1<i>H</i>-1,2,3-triazole-4-yl) methoxy functionalized pyridine derivatives <b>5</b> and <b>6</b> have been prepared starting from 2(1<i>H</i>) pyridone <b>1</b> <i>via</i> selective <i>O-</i>propargylation followed by reaction with diverse substituted azides under Sharpless conditions. All the compounds <b>5</b> and <b>6</b> have been screened for antimicrobial activity, minimum bactericidal concentration and biofilm inhibition activity. Compounds <b>5d</b>, <b>5l</b> and <b>5s</b> which showed promising activity specifically towards <i>Staphylococcus aureus</i> MTCC 96 and <i>Staphylococcus aureus</i> MLS-16 MTCC 2940 have been identified. Further, <i>in silico</i> docking studies have been carried out on the inhibition of dehydrosqualene synthase enzyme of <i>S. aureus</i>. This is a key enzyme in the biosynthesis of staphyloxanthin, a virulence factor for <i>S. aureus</i>. Further, on screening for antioxidant activity, the compounds <b>5l</b>, <b>5q</b> and <b>5n</b> showed promising activity.