Anti-staphylococcal activity and mode of action of thioridazine photoproducts
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10362/116489 |
Resumo: | 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. |
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Anti-staphylococcal activity and mode of action of thioridazine photoproductsBiochemistry, Genetics and Molecular Biology (miscellaneous)Drug DiscoveryMicrobiologyInfectious DiseasesSDG 3 - Good Health and Well-beingAntibiotic 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.Instituto de Higiene e Medicina Tropical (IHMT)TB, HIV and opportunistic diseases and pathogens (THOP)Global Health and Tropical Medicine (GHTM)RUNTozar, TatianaSantos Costa, SofiaUdrea, Ana MariaNastasa, ViorelCouto, IsabelViveiros, MiguelPascu, Mihail LucianRomanitan, Mihaela Oana2021-04-30T22:42:54Z2020-12-012020-12-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttp://hdl.handle.net/10362/116489eng2045-2322PURE: 26185645https://doi.org/10.1038/s41598-020-74752-zinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:59:05Zoai:run.unl.pt:10362/116489Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:43:05.259291Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
title |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
spellingShingle |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts Tozar, Tatiana Biochemistry, Genetics and Molecular Biology (miscellaneous) Drug Discovery Microbiology Infectious Diseases SDG 3 - Good Health and Well-being |
title_short |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
title_full |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
title_fullStr |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
title_full_unstemmed |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
title_sort |
Anti-staphylococcal activity and mode of action of thioridazine photoproducts |
author |
Tozar, Tatiana |
author_facet |
Tozar, Tatiana Santos Costa, Sofia Udrea, Ana Maria Nastasa, Viorel Couto, Isabel Viveiros, Miguel Pascu, Mihail Lucian Romanitan, Mihaela Oana |
author_role |
author |
author2 |
Santos Costa, Sofia Udrea, Ana Maria Nastasa, Viorel Couto, Isabel Viveiros, Miguel Pascu, Mihail Lucian Romanitan, Mihaela Oana |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Instituto de Higiene e Medicina Tropical (IHMT) TB, HIV and opportunistic diseases and pathogens (THOP) Global Health and Tropical Medicine (GHTM) RUN |
dc.contributor.author.fl_str_mv |
Tozar, Tatiana Santos Costa, Sofia Udrea, Ana Maria Nastasa, Viorel Couto, Isabel Viveiros, Miguel Pascu, Mihail Lucian Romanitan, Mihaela Oana |
dc.subject.por.fl_str_mv |
Biochemistry, Genetics and Molecular Biology (miscellaneous) Drug Discovery Microbiology Infectious Diseases SDG 3 - Good Health and Well-being |
topic |
Biochemistry, Genetics and Molecular Biology (miscellaneous) Drug Discovery Microbiology Infectious Diseases SDG 3 - Good Health and Well-being |
description |
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. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-12-01 2020-12-01T00:00:00Z 2021-04-30T22:42:54Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/116489 |
url |
http://hdl.handle.net/10362/116489 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2045-2322 PURE: 26185645 https://doi.org/10.1038/s41598-020-74752-z |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
12 application/pdf |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799138041279807488 |