Synthesis of Coumarin-Triazene-Alkoxyphenyl Derivatives and In Silico Simulation for Potential Antimicrobial Activity

The use of antibiotics is causing rapid growth of antibiotic-resistant bacteria. This can result in significant challenges for controlling pathogenic diseases in the future. The search for new potential antimicrobial compounds is critical, and natural-based scaffolds such as coumarin offer promising lead compounds for the development of new antibacterial compounds through structural hybridization. This study aims to synthesize coumarin-triazene-alkoxyphenyl hybrids 4a-4c bearing a long alkoxy chain and evaluate their antimicrobial potential via docking simulation. The synthesis started with the preparation of alkoxyanilines 2a-2c and cyanocoumarin 3 as precursors under microwave irradiation, resulting in a better yield (68-82 and 61%, respectively) in a few minutes. Diazo coupling reaction of 2a-2c and 3 produced coumarin-triazene hybrids 4a-4c with 47-63% yield. In silico simulation showed that compound 4a had a binding affinity (-6.7 kcal/mol) toward bacterial DNA gyrase similar to clorobiocin as reference compound, which indicates its potential to influence and inhibit the activity of the bacterial enzyme. These preliminary findings could establish a useful basis for discovering new antimicrobial compounds through derivatization or modification of the coumarin scaffold.