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Based on previous research from these laboratories various structural analogs of 3-hydroxyflavone were tested for inhibition of glyoxalase 1 (S-lactoyl-glutathione methylglyoxal lyase, isomerizing; EC 4.4.1.5). The substrate of glyoxalase I (Glo I), methylglyoxal, has growth inhibitory properties. Glo I was purified 7000-fold from human red blood cells, and the concentration of various flavones was determined for 50% inhibition

Previous reports from these laboratories on the inhibition of glyoxalase I (S-lactoyl-glutathione methylglyoxal lyase, isomerizing; EC 4.4.1.5) (Glo I) have been presented for various flavones and other compounds. We report here the inhibition of Glo I by coumarin and various coumarin derivatives. Human red blood cell Glo I was purified 7000-fold and the concentration of various coumarins was determined for 50% inhibition (I,) of enzyme activity. These compounds resemble the transition state of the methylglyoxal hemimercaptal as previously reported. The I, varies from 3.5 pA4 to I .9 mM for the compounds tested with the parent compound coumarin having an I, of 1.9 mM. 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.