Quinine and Quinidine Derivatives as Photosensitizers for Photodynamic Inactivation of Bacterial Pathogens

奎宁和奎尼丁衍生物作为光敏剂用于光动力灭活细菌病原体

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Abstract

This study reports the synthesis and characterization of 5-azoniabenzo[no]tetraphene derivatives of Cinchona alkaloids with potential applications in antimicrobial photodynamic therapy (aPDT). These compounds exhibit absorption maxima at 430-441 nm, as well as in the UV-A (340-342 nm) and UV-C (270-275 nm) regions, with fluorescence emission peaks ranging from 519 to 534 nm. At nontoxic concentrations of 2 μg mL(-1) and upon irradiation with blue light (418 nm), these compounds demonstrated potent bactericidal activity depending on the light dose. Staphylococcus aureus was eradicated after 5 min of irradiation (50 J cm(-2)) with the isomer of 7R,2'S configuration (QN-1) as a photosensitizer. Gram-negative bacteria exhibited reduced sensitivity, with Acinetobacter baumannii requiring an energy dose of 150 J cm(-2) for effective killing, whereas Proteus mirabilis showed no significant reduction after exposure to 200 J cm(-2). The differences in sensitivity are attributed to the structure of the cell envelopes, which influence the uptake of the photosensitizer: the compounds accumulated intracellularly in Gram-positive bacteria but remained extracellular in Gram-negative rods. It is suggested that the aPDT mechanism involves a combination of oxidative pathways for QN-1 and QD-1 as photosensitizers and a Type II mechanism when QN-2 was applied.

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