In Vitro Inhibition of Glyoxalase І by Flavonoids: New Insights from Crystallographic Analysis

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 (K_i 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.

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