Development of sulfahydantoin derivatives as ß-lactamase inhibitors.
Bioorg Med Chem Lett
; 35: 127781, 2021 03 01.
Article
em En
| MEDLINE
| ID: mdl-33422604
ABSTRACT
Sulfahydantoin-based molecules may provide a means to counteract antibiotic resistance, which is on the rise. These molecules may act as inhibitors of ß-lactamase enzymes, which are key in some resistance mechanisms. In this paper, we report on the synthesis of 6 novel sulfahydantoin derivatives by the key reaction of chlorosulfonyl isocyanate to form α-amino acid derived sulfamides, and their cyclization into sulfahydantoins. The synthesis is rapid and provides the target compounds in 8 steps. We investigated their potential as ß-lactamase inhibitors using two common Class A ß-lactamases, TEM-1 and the prevalent extended-spectrum TEM-15. Two compounds, 3 and 6, show substantial inhibition of the ß-lactamases with IC50 values between 130 and 510 µM and inferred Ki values between 32 and 55 µM.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Compostos de Enxofre
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Beta-Lactamases
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Inibidores de beta-Lactamases
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Desenvolvimento de Medicamentos
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article