Next-Generation Heterocyclic Electrophiles as Small-Molecule Covalent MurA Inhibitors.
Pharmaceuticals (Basel)
; 15(12)2022 Nov 29.
Article
em En
| MEDLINE
| ID: mdl-36558935
ABSTRACT
Heterocyclic electrophiles as small covalent fragments showed promising inhibitory activity on the antibacterial target MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase, EC2.5.1.7). Here, we report the second generation of heterocyclic electrophiles the quaternized analogue of the heterocyclic covalent fragment library with improved reactivity and MurA inhibitory potency. Quantum chemical reaction barrier calculations, GSH (L-glutathione) reactivity assay, and thrombin counter screen were also used to demonstrate and explain the improved reactivity and selectivity of the N-methylated heterocycles and to compare the two generations of heterocyclic electrophiles.
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Bases de dados:
MEDLINE
Idioma:
En
Revista:
Pharmaceuticals (Basel)
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Hungria