Synthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains

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Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorThe University of Auckland-
Autor(es): dc.contributorUniversity College London-
Autor(es): dc.creatorFernandes, Guilherme F. S.-
Autor(es): dc.creatorManieri, Karyn F.-
Autor(es): dc.creatorBonjorno, Andressa F.-
Autor(es): dc.creatorCampos, Debora L.-
Autor(es): dc.creatorRibeiro, Camila M.-
Autor(es): dc.creatorDemarqui, Fernanda M.-
Autor(es): dc.creatorRuiz, Daniel A. G.-
Autor(es): dc.creatorNascimento-Junior, Nailton M.-
Autor(es): dc.creatorDenny, William A.-
Autor(es): dc.creatorThompson, Andrew M.-
Autor(es): dc.creatorPavan, Fernando R.-
Autor(es): dc.creatorDos Santos, Jean L.-
Data de aceite: dc.date.accessioned2025-08-21T23:18:31Z-
Data de disponibilização: dc.date.available2025-08-21T23:18:31Z-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2023-07-29-
Data de envio: dc.date.issued2022-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.1002/cmdc.202300015-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/249879-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/249879-
Descrição: dc.descriptionThe emergence of multidrug-resistant strains of M. tuberculosis has raised concerns due to the greater difficulties in patient treatment and higher mortality rates. Herein, we revisited the 2-nitro-6,7-dihydro-5H-imidazo[2,1-b][1,3]oxazine scaffold and identified potent new carbamate derivatives having MIC90 values of 0.18–1.63 μM against Mtb H37Rv. Compounds 47–49, 51–53, and 55 exhibited remarkable activity against a panel of clinical isolates, displaying MIC90 values below 0.5 μM. In Mtb-infected macrophages, several compounds demonstrated a 1-log greater reduction in mycobacterial burden than rifampicin and pretomanid. The compounds tested did not exhibit significant cytotoxicity against three cell lines or any toxicity to Galleria mellonella. Furthermore, the imidazo[2,1-b][1,3]oxazine derivatives did not show substantial activity against other bacteria or fungi. Finally, molecular docking studies revealed that the new compounds could interact with the deazaflavin-dependent nitroreductase (Ddn) in a similar manner to pretomanid. Collectively, our findings highlight the chemical universe of imidazo[2,1-b][1,3]oxazines and their promising potential against MDR-TB.-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University, Rod. Araraquara-Jaú-
Descrição: dc.descriptionAuckland Cancer Society Research Centre Faculty of Medical and Health Sciences The University of Auckland, Private Bag 92019-
Descrição: dc.descriptionInstitute of Chemistry São Paulo State University, Rua Professor Francisco Degni, 55-
Descrição: dc.descriptionDepartment of Chemistry University College London, 20 Gordon Street-
Descrição: dc.descriptionSchool of Pharmaceutical Sciences São Paulo State University, Rod. Araraquara-Jaú-
Descrição: dc.descriptionInstitute of Chemistry São Paulo State University, Rua Professor Francisco Degni, 55-
Idioma: dc.languageen-
Relação: dc.relationChemMedChem-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subject2-nitroimidazooxazine-
Palavras-chave: dc.subjectImidazo[2,1-b][1,3]oxazine-
Palavras-chave: dc.subjectmultidrug-resistant tuberculosis-
Palavras-chave: dc.subjectpretomanid derivatives-
Palavras-chave: dc.subjecttuberculosis-
Título: dc.titleSynthesis and Anti-Mycobacterium tuberculosis Activity of Imidazo[2,1-b][1,3]oxazine Derivatives against Multidrug-Resistant Strains-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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