Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress

Detalhes bibliográficos
Autor(a) principal: da Silva, Emerson Rodrigo [UNIFESP]
Data de Publicação: 2022
Outros Autores: Valêncio, André [UNIFESP], Machado, Marcelo Ferreira Marcondes [UNIFESP], Miranda, Antonio [UNIFESP]
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
dARK ID: ark:/48912/001300000q7m9
DOI: 10.1002/slct.202203032
Texto Completo: https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202203032
https://repositorio.unifesp.br/handle/11600/67461
Resumo: Cephalexin is a beta-lactam antibiotic of the first generation of cephalosporins which is very effective against various bacterial infections. In this work, we investigate the structure and antibacterial activity of cephalexin solutions submitted to forced degradation under heat stress and photolytic irradiation. A combination of analytical techniques gathering LC/ESI-MS and NMR spectroscopy allowed us to identify different chemical species amongst the byproducts, revealing that photolysis via UV light leads to significant amounts of oxidized species that conserve the dihydrothiazine ring adjacent to the beta-lactam ring. In contrast, thermodegradation induces the rupture of the bioactive moiety possibly with the production of cephalosporinic acid and deaminated species, which are inactive to bacteria. Microbiological analyses using E. coli as a model organism indicated that the antimicrobial capacity of samples submitted to thermolysis is suppressed while solutions submitted to irradiation with UVA light preserve their bactericidal power. Atomic force microscopy showed that cells incubated with photodegraded cephalexin are much longer than those incubated with the undegraded antibiotic, indicating that byproducts from photolysis inhibit septum formation and likely affect the action of penicillin-binding protein 3 in the divisome of E. coli cells.
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spelling Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stressAntibioticsDegradationCephalosporinsPhotolysisCephalexin is a beta-lactam antibiotic of the first generation of cephalosporins which is very effective against various bacterial infections. In this work, we investigate the structure and antibacterial activity of cephalexin solutions submitted to forced degradation under heat stress and photolytic irradiation. A combination of analytical techniques gathering LC/ESI-MS and NMR spectroscopy allowed us to identify different chemical species amongst the byproducts, revealing that photolysis via UV light leads to significant amounts of oxidized species that conserve the dihydrothiazine ring adjacent to the beta-lactam ring. In contrast, thermodegradation induces the rupture of the bioactive moiety possibly with the production of cephalosporinic acid and deaminated species, which are inactive to bacteria. Microbiological analyses using E. coli as a model organism indicated that the antimicrobial capacity of samples submitted to thermolysis is suppressed while solutions submitted to irradiation with UVA light preserve their bactericidal power. Atomic force microscopy showed that cells incubated with photodegraded cephalexin are much longer than those incubated with the undegraded antibiotic, indicating that byproducts from photolysis inhibit septum formation and likely affect the action of penicillin-binding protein 3 in the divisome of E. coli cells.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)19/20907-7Willeyhttp://lattes.cnpq.br/7800589206457326http://lattes.cnpq.br/0596334947896054http://lattes.cnpq.br/9703373400186586http://lattes.cnpq.br/1357848049935882Lourenço, CecíliaSouza, Louise E. A.da Silva, Emerson Rodrigo [UNIFESP]Valêncio, André [UNIFESP]Machado, Marcelo Ferreira Marcondes [UNIFESP]Miranda, Antonio [UNIFESP]2023-05-08T17:22:54Z2023-05-08T17:22:54Z2022-11-21info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersione202203032application/pdfhttps://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202203032https://repositorio.unifesp.br/handle/11600/67461ark:/48912/001300000q7m9engChemistrySelectinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-12T16:23:54Zoai:repositorio.unifesp.br/:11600/67461Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-12-11T20:30:48.474138Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
title Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
spellingShingle Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
da Silva, Emerson Rodrigo [UNIFESP]
Antibiotics
Degradation
Cephalosporins
Photolysis
da Silva, Emerson Rodrigo [UNIFESP]
Antibiotics
Degradation
Cephalosporins
Photolysis
title_short Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
title_full Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
title_fullStr Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
title_full_unstemmed Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
title_sort Molecular structure and antibacterialactivity of degradation products from cephalexin solutions submitted to thermal and photolytic stress
author da Silva, Emerson Rodrigo [UNIFESP]
author_facet da Silva, Emerson Rodrigo [UNIFESP]
da Silva, Emerson Rodrigo [UNIFESP]
Valêncio, André [UNIFESP]
Machado, Marcelo Ferreira Marcondes [UNIFESP]
Miranda, Antonio [UNIFESP]
Valêncio, André [UNIFESP]
Machado, Marcelo Ferreira Marcondes [UNIFESP]
Miranda, Antonio [UNIFESP]
author_role author
author2 Valêncio, André [UNIFESP]
Machado, Marcelo Ferreira Marcondes [UNIFESP]
Miranda, Antonio [UNIFESP]
author2_role author
author
author
dc.contributor.none.fl_str_mv http://lattes.cnpq.br/7800589206457326
http://lattes.cnpq.br/0596334947896054
http://lattes.cnpq.br/9703373400186586
http://lattes.cnpq.br/1357848049935882
Lourenço, Cecília
Souza, Louise E. A.
dc.contributor.author.fl_str_mv da Silva, Emerson Rodrigo [UNIFESP]
Valêncio, André [UNIFESP]
Machado, Marcelo Ferreira Marcondes [UNIFESP]
Miranda, Antonio [UNIFESP]
dc.subject.por.fl_str_mv Antibiotics
Degradation
Cephalosporins
Photolysis
topic Antibiotics
Degradation
Cephalosporins
Photolysis
description Cephalexin is a beta-lactam antibiotic of the first generation of cephalosporins which is very effective against various bacterial infections. In this work, we investigate the structure and antibacterial activity of cephalexin solutions submitted to forced degradation under heat stress and photolytic irradiation. A combination of analytical techniques gathering LC/ESI-MS and NMR spectroscopy allowed us to identify different chemical species amongst the byproducts, revealing that photolysis via UV light leads to significant amounts of oxidized species that conserve the dihydrothiazine ring adjacent to the beta-lactam ring. In contrast, thermodegradation induces the rupture of the bioactive moiety possibly with the production of cephalosporinic acid and deaminated species, which are inactive to bacteria. Microbiological analyses using E. coli as a model organism indicated that the antimicrobial capacity of samples submitted to thermolysis is suppressed while solutions submitted to irradiation with UVA light preserve their bactericidal power. Atomic force microscopy showed that cells incubated with photodegraded cephalexin are much longer than those incubated with the undegraded antibiotic, indicating that byproducts from photolysis inhibit septum formation and likely affect the action of penicillin-binding protein 3 in the divisome of E. coli cells.
publishDate 2022
dc.date.none.fl_str_mv 2022-11-21
2023-05-08T17:22:54Z
2023-05-08T17:22:54Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202203032
https://repositorio.unifesp.br/handle/11600/67461
dc.identifier.dark.fl_str_mv ark:/48912/001300000q7m9
url https://chemistry-europe.onlinelibrary.wiley.com/doi/full/10.1002/slct.202203032
https://repositorio.unifesp.br/handle/11600/67461
identifier_str_mv ark:/48912/001300000q7m9
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv ChemistrySelect
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv e202203032
application/pdf
dc.publisher.none.fl_str_mv Willey
publisher.none.fl_str_mv Willey
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1822183930925678592
dc.identifier.doi.none.fl_str_mv 10.1002/slct.202203032