The antitumor pharmacological property of flavonoids is correlated with
inhibition towards glyoxalase I (GLOI), a critical zinc-enzyme in the methylglyoxal
detoxification pathway. In this study, 16 flavonoids were examined, and only baicalein
(Ki of 0.183 µM) is identified as a potent in vitro GLOI inhibitor. X-ray crystallographic
analysis reveals that baicalein chelates with the catalytic Zn2+ via its characteristic
C6/C7 hydroxyl groups. The coordination ability of flavonoids, and therefore
their ability to inhibit GLOI, is determined by the Zn2+ coordination geometry, the
rigid skeleton of flavonoids and the geometry of the hydrophobic cavity of the GLOI
active site. This structural basis could be useful in predicting GLOI inhibition of other natural polyphenols.
Keywords: Baicalein, Crystal structure, Flavonoids, Glyoxalase I, Inhibition.
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