Novel photoactivated Indole–pyridine chemotherapeutics with strong antimicrobial and antibiofilm activity toward Staphylococcus aureus.

Novel chemotherapeutics photo-inactivate Staphylococcus aureus and destruct Staphylococcus aureus bioflim through type I and type II mehcanism of photodyanmic therapy. Photocatalysis of NAD(P)H upon white light irradiation may contribute to its excellent antimicrobial activity. [Display omitted] • The cationic photosensitizers was designed for photo-induced antimicrobial and antibiofilm activity towards free Staphylococcus aureus and biofilm. The most effective compound exhibited multiple type I/II photosensitization and coenzyme NAD(P)H photocatalytic activity upon excitation, causing membrane damage and protein/nucleus acids leakage. The challenge of antibiotic resistance worldwide has brought an urgent need to explore novel drugs for bacterial infections. Antimicrobial photodynamic therapy has been proven to be a potential antimicrobial modality but is limited by biofilms. In this study, we synthesized three cationic photosensitizers with strong photoinduced antimicrobial and antibiofilm activities toward gram-positive Staphylococcus aureus. The indole–pyridine compounds illustrated multiple type I/II photosensitization and coenzyme NAD(P)H photocatalytic activity upon excitation. A mechanistic study showed that intracellular reactive oxygen generation and NAD(P)H oxidation caused membrane damage, leading to protein/nucleus acid leakage. This research provides insights into the development of novel chemotherapeutics with synergetic photodynamic and photocatalytic reactivity. [ABSTRACT FROM AUTHOR]