Next-Generation Heterocyclic Electrophiles as Small-Molecule Covalent MurA Inhibitors.

ABSTRACT: Heterocyclic electrophiles as small covalent fragments showed promising inhibitory activity on the antibacterial target MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase, EC:2.5.1.7). 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.

SUBMITTER: Abranyi-Balogh P 

PROVIDER: S-EPMC9781958 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature