Theoretical investigations of the structure of potential inhibitors of the enzyme glyoxalase-I

Abstract

Ab initio calculations using an sm3G basis set are reported for a variety of known inhibitors of glyoxalase I (esculetin, isoesculetin, ascorbic acid, maltol, etc.). Experimental investigations suggest that these inhibitors function as transition state analogs; and molecular electrostatic potential maps of the substrate of the enzyme, a variety of possible intermediates, and the inhibitors were calculated and compared. It was found that the most effective inhibitors have the distance R between the OH minima of -3.4 A. Suggestions for other inhibitors are made on the basis of the calculations.

Inhibition of glyoxalase I in vitro by coumarin and coumarin derivatives

“…The most inhibitory compounds had hydroxyls at various positions on the coumarin ring system and a phenyl or similar group at the 3 or 4 position on the pyrone ring. Molecular electrostatic potential maps were calculated for three of the compounds tested and they provide suggestive evidence for the inhibitory regions of the molecules.were selected on the basis of their fitting the role of transition-state intermediates in the Glo I system [5].We report here in brief the synthesis of a number of coumarin derivatives and their inhibition of purified human red blood cell Glo I activity with their concentration for 50% inhibition (Iso) and the type of inhibition exhibited.…”

“…were selected on the basis of their fitting the role of transition-state intermediates in the Glo I system [5].…”