External oxidant-free and transition metal-free synthesis of 5-amino-1,2,4-thiadiazoles as promising antibacterials against ESKAPE pathogen strains.
Mol Divers
; 27(2): 651-666, 2023 Apr.
Article
em En
| MEDLINE
| ID: mdl-35639224
ABSTRACT
A new route to 5-amino-1,2,4-thiadiazole derivatives via reaction of N-chloroamidines with isothiocyanates has been proposed. The advantages of this method are high product yields (up to 93%), the column chromatography-free workup procedure, scalability and the absence of additive oxidizing agents or transition metal catalysts. The 28 examples of 5-amino-1,2,4-thiadiazole derivatives obtaining via the proposing protocol were evaluated in vitro against ESKAPE pathogens strains (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter cloacae). It was found that compounds 5ba, 5bd, 6a, 6d and 6c have potent antibacterial activity (MIC values 0.09-1.5 µg mL-1), which is superior to the activity of commercial antibiotics such as pefloxacin (MIC 4-8 µg mL-1) and streptomycin (MIC 2-32 µg mL-1). The additional cytotoxic assay of hit compounds on PANC-1 cell line demonstrated the low or non-cytotoxicity activity at the same level of concentrations. Thus, these 5 compounds are promising starting point for further antimicrobial drug development.
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Base de dados:
MEDLINE
Assunto principal:
Enterococcus faecium
/
Anti-Infecciosos
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article