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tert-Butylphenylthiazoles with an oxadiazole linker: a novel orally bioavailable class of antibiotics exhibiting antibiofilm activity

The structure–activity and structure–kinetic relationships of a new tert-butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds. Twenty-two new compounds were prepared, purified and identified. Their activity a...

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Detalles Bibliográficos
Autores principales: Kotb, Ahmed, Abutaleb, Nader S., Hagras, Mohamed, Bayoumi, Ashraf, Moustafa, Mahmoud M., Ghiaty, Adel, Seleem, Mohamed N., Mayhoub, Abdelrahman S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society of Chemistry 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9061097/
https://www.ncbi.nlm.nih.gov/pubmed/35518469
http://dx.doi.org/10.1039/c8ra10525a
Descripción
Sumario:The structure–activity and structure–kinetic relationships of a new tert-butylphenylthiazole series with oxadiazole linkers were conducted with the objective of obtaining a new orally available antibacterial compounds. Twenty-two new compounds were prepared, purified and identified. Their activity against methicillin-resistant Staphylococcus aureus were examined. Compound 20 with 3-hydroxyazetidine as a nitrogenous side chain showed promising activity against twenty-four clinical isolates, including vancomycin-resistant staphylococcal and enterococcal species with MIC values ranging from 4–8 μg mL(−1). Additional advantages of this compound include an ability to eradicate staphylococcal biofilm mass in a dose-dependent manner as well as high metabolic stability after an oral dose of 25 mg kg(−1) with a biological half-life that exceeds 5 hours and a plasma concentration (C(max)) that exceeds the MIC values.