Synthesis and evaluation of novel ring-conjugated coumarins as biosafe broad-spectrum antimicrobial candidates

Abstract

This study presents, for the first time, the synthesis of innovative conjugates identified as a five-membered ring integrating three heteroatoms linked linearly to the coumarin framework. Seven conjugates, comprising combinations of 1,3,2-dioxathiole-2-oxide and coumarin derivatives, were made via a three-stage synthetic procedure originating from benzene 1,2,4-triole. Spectroscopic methodologies, encompassing 1H-NMR, 13C-NMR, and FTIR, were utilized to validate the structural frameworks of the synthesized conjugates. Their capacity in the biomedicine field to act as broad-spectrum antimicrobial agents was evaluated. Furthermore, the biosafety and in silico pharmacokinetic characteristics of the conjugates were also examined. Six pathogenic aerobic bacteriomers, three anaerobic bacteriomers, and two fungiomers were utilized to investigate the broad-spectrum antimicrobial activity of the conjugates. On the other hand, three non-pathogenic bacteriomers were employed to reveal the biosafety profiles of the synthesized conjugates. Finally, two web-based programs were utilized to unveil the pharmacokinetic profiles of the title conjugates. The authors outlined four principal outcomes drawn from the extracted results. The conjugation between 1,3,2-dioxathiole-2-oxide and coumarin derivatives demonstrates biosafety and broad-spectrum antimicrobial implications. Conjugate DOTC5 displayed potent antibacterial activity against the tested aerobic bacteriomers, showing a potency comparable to that of the reference drug. Conjugate DOTC1 demonstrated strong antifungal activity exceeding that of the standard used. The synthesized conjugates, particularly DOTC5, displayed interesting biosafety profiles against the non-pathogenic bacteriomers. It concluded that the conjugates DOTC5 and DOTC1 exhibit the potential to function as valuable scaffolds for developing novel medications with biosafe, broad-spectrum antimicrobial activities in the foreseeable future.