Anti-staphylococcal activity and mode of action of thioridazine photoproducts

Tatiana Tozar, Sofia Santos Costa, Ana Maria Udrea, Viorel Nastasa, Isabel Couto, Miguel Viveiros, Mihail Lucian Pascu, Mihaela Oana Romanitan

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)
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Antibiotic resistance became an increasing risk for population health threatening our ability to fight infectious diseases. The objective of this study was to evaluate the activity of laser irradiated thioridazine (TZ) against clinically-relevant bacteria in view to fight antibiotic resistance. TZ in ultrapure water solutions was irradiated (1–240 min) with 266 nm pulsed laser radiation. Irradiated solutions were characterized by UV–Vis and FTIR absorption spectroscopy, thin layer chromatography, laser-induced fluorescence, and dynamic surface tension measurements. Molecular docking studies were made to evaluate the molecular mechanisms of photoproducts action against Staphylococcus aureus and MRSA. More general, solutions were evaluated for their antimicrobial and efflux inhibitory activity against a panel of bacteria of clinical relevance. We observed an enhanced antimicrobial activity of TZ photoproducts against Gram-positive bacteria. This was higher than ciprofloxacin effects for methicillin- and ciprofloxacin-resistant Staphylococcus aureus. Molecular docking showed the Penicillin-binding proteins PBP3 and PBP2a inhibition by sulforidazine as a possible mechanism of action against Staphylococcus aureus and MRSA strains, respectively. Irradiated TZ reveals possible advantages in the treatment of infectious diseases produced by antibiotic-resistant Gram-positive bacteria. TZ repurposing and its photoproducts, obtained by laser irradiation, show accelerated and low-costs of development if compared to chemical synthesis.

Original languageEnglish
Article number18043
Pages (from-to)18043-18055
Number of pages12
JournalScientific Reports
Issue number1
Publication statusPublished - 1 Dec 2020


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