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 (-glutathione) reactivity assay, and thrombin counter screen were also used to demonstrate and explain the improved reactivity and selectivity of the -methylated heterocycles and to compare the two generations of heterocyclic electrophiles.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9781958PMC
http://dx.doi.org/10.3390/ph15121484DOI Listing

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