Anti-staphylococcal activity and mode of action of thioridazine photoproducts

Autor: Ana-Maria Udrea, Mihail Lucian Pascu, Tatiana Tozar, Viorel Nastasa, Mihaela Oana Romanitan, Isabel Couto, Miguel Viveiros, Sofia Santos Costa
Přispěvatelé: Instituto de Higiene e Medicina Tropical (IHMT), TB, HIV and opportunistic diseases and pathogens (THOP), Global Health and Tropical Medicine (GHTM)
Jazyk: angličtina
Rok vydání: 2020
Předmět:
0301 basic medicine
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus
Bioinformatics
030106 microbiology
Optical spectroscopy
lcsh:Medicine
medicine.disease_cause
Antimicrobial resistance
Biochemistry
Genetics and Molecular Biology (miscellaneous)
Microbiology
Article
03 medical and health sciences
Antibiotic resistance
SDG 3 - Good Health and Well-being
Drug Discovery
Drug Resistance
Bacterial
medicine
Mode of action
Fluorescence spectroscopy
lcsh:Science
Infrared spectroscopy
Multidisciplinary
biology
Chemistry
Thioridazine
Antimicrobials
Lasers
Biological techniques
lcsh:R
Drug Repositioning
Water
biology.organism_classification
Antimicrobial
Sulforidazine
Anti-Bacterial Agents
Ciprofloxacin
Solutions
030104 developmental biology
Infectious Diseases
Spectrophotometry
lcsh:Q
Efflux
Bacteria
medicine.drug
Antipsychotic Agents
Zdroj: Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020)
Scientific Reports
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 2045-2322
DOI: 10.1038/s41598-020-74752-z
Popis: 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.
Databáze: OpenAIRE
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