Abstract
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.
Graphical Abstract
Current Topics in Medicinal Chemistry
Title:In Vitro Inhibition of Glyoxalase І by Flavonoids: New Insights from Crystallographic Analysis
Volume: 16 Issue: 4
Author(s): Hong Zhang, Jing Zhai, Liping Zhang, Cuiyun Li, Yining Zhao, Yunyun Chen, Qing Li and Xiao Peng Hu
Affiliation:
Keywords: Baicalein, Crystal structure, Flavonoids, Glyoxalase I, Inhibition.
Abstract: 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.
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Cite this article as:
Zhang Hong, Zhai Jing, Zhang Liping, Li Cuiyun, Zhao Yining, Chen Yunyun, Li Qing and Hu Peng Xiao, In Vitro Inhibition of Glyoxalase І by Flavonoids: New Insights from Crystallographic Analysis, Current Topics in Medicinal Chemistry 2016; 16 (4) . https://dx.doi.org/10.2174/1568026615666150813150944
DOI https://dx.doi.org/10.2174/1568026615666150813150944 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
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