New D‐π‐A‐Based Coumarin‐ Derived Fluorescent Theranostic Probes With Broad‐Spectrum Antimicrobial Activity

ABSTRACT Understanding how multidrug‐resistant (MDR) bacteria and fungi defy the existing antimicrobial agents requires innovative tools and techniques for real‐time, in situ exploration of bacterial responses to antibiotics. Fluorescence‐tagged antibiotics or dyes with inherent antimicrobial activity can provide a profound understanding of the molecular biology underlying antibiotic action and resistance mechanisms. Cutting‐edge research highlights the pursuit of benzo‐α‐pyrone (coumarin) derivatives due to their excellent pharmacokinetics, diverse pharmacological activities, and innovative fluorescence molecular probes. In this study, donor‐π‐acceptor‐based coumarin dyes were designed and evaluated for antimicrobial efficacy against fungal strains ( Candida albicans ), Gram‐negative pathogens ( Escherichia coli ), and Gram‐positive bacteria ( Staphylococcus aureus ). I‐6 exhibited notable antimicrobial activity against S. aureus and C. albicans compared with E. coli . Conversely, I‐9, a congener of I‐6, showed a comparable affinity for S. aureus but found poor activity against the remaining tested strains. Mechanistic investigative studies unveiled that the inhibitory efficacy of I‐6 can be attributed to its capacity to generate high reactive oxygen species (ROS) formation. Despite the evident antimicrobial potential of I‐6 in the data, our future prospects, including real‐time visualization to study physiological processes like uptake, distribution, and mechanism of action through fluorescence‐based imaging modalities, could enhance the applicability of these probes.