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Inhibition of glyoxalase I in vitro by coumarin and coumarin derivatives
Author(s) -
Brandt Richard B.,
Laux Jerome E.,
Yates Steven W.,
Boots Marvin R.,
Thomson Colin,
Edge Colin
Publication year - 2009
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560300816
Subject(s) - coumarin , chemistry , in vitro , lactoylglutathione lyase , biochemistry , methylglyoxal , organic chemistry , enzyme
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 50 ) of enzyme activity. These compounds resemble the transition state of the methylglyoxal hemimercaptal as previously reported. The I 50 varies from 3.5 m̈ M to 1.9 m M for the compounds tested with the parent compound coumarin having an I 50 of 1.9 m M . 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.