Synthesis and Evaluation of New Coumarin Derivatives as Antioxidant, Antimicrobial, and Anti-Inflammatory Agents

Abstract

New pyranocoumarin and coumarin-sulfonamide derivatives were prepared and evaluated for their antioxidant, antimicrobial, and/or anti-inflammatory activities. Coumarin-sulfonamide compounds <b>8a-d</b> demonstrated significant antioxidant activity, while <b>7c</b>,<b>d</b>, <b>8c</b>,<b>d</b>, and <b>9c</b>,<b>d</b> exhibited antimicrobial activity equal to or higher than the standard antimicrobials against at least one tested microorganism. Regarding the anti-inflammatory testing, pyranocoumarins <b>2b</b>, <b>3a</b>,<b>b</b> and <b>5c</b> and coumarin-sulfonamide compound <b>9a</b> showed more potent antiproteinase activity than aspirin in vitro; however, five compounds were as potent as aspirin. The anti-inflammatory activity of the promising compounds was further assessed pharmacologically on formaldehyde-induced rat paw oedema and showed significant inhibition of oedema. For in vitro COX-inhibitory activity of coumarin derivatives, pyranocoumarin derivative <b>5a</b> was the most selective (SI = 152) and coumarin-sulfonamide derivative <b>8d</b> was most active toward COX-2 isozyme. The most active derivatives met the in silico criteria for orally active drugs; thus, they may serve as promising candidates to develop more potent and highly efficient antioxidant, antimicrobial, and/or anti-inflammatory agents.