Related Experiment Video
Updated: Aug 16, 2025

Functionalized Spirocyclic Heterocycle Synthesis and Cytotoxicity Assay
Published on: February 9, 2021
Next-Generation Heterocyclic Electrophiles as Small-Molecule Covalent MurA Inhibitors
Péter Ábrányi-Balogh1, Aaron Keeley1, György G Ferenczy1
1Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Magyar tudósok krt 2, H-1117 Budapest, Hungary.
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.
Related Concept Videos
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Five-Membered Heterocyclic Aromatic Compounds: Overview
ortho–para-Directing Deactivators: Halogens
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
Cycloaddition Reactions: MO Requirements for Photochemical Activation
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...

