Structure–Activity Relationship of Xanthones as Inhibitors of Xanthine Oxidase

Abstract

Polygala plants contain a large number of xanthones with good physiological activities. In our previous work, 18 xanthones were isolated from Polygala crotalarioides. Extented study of the chemical composition of the other species Polygala sibirica led to the separation of two new xanthones—3-hydroxy-1,2,6,7,8-pentamethoxy xanthone (A) and 6-O-β-d-glucopyranosyl-1,7-dimethoxy xanthone (C)—together with 14 known xanthones. Among them, some xanthones have a certain xanthine oxidase (XO) inhibitory activity. Furthemore, 14 xanthones as XO inhibitors were selected to develop three-dimensional quantitative structure–activity relationship (3D-QSAR) using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) models. The CoMFA model predicted a q2 value of 0.613 and an r2 value of 0.997. The best CoMSIA model predicted a q2 value of 0.608 and an r2 value of 0.997 based on a combination of steric, electrostatic, and hydrophobic effects. The analysis of the contour maps from each model provided insight into the structural requirements for the development of more active XO inhibitors.

<p>Anti-Tumor Xanthones from <em>Garcinia nujiangensis</em> Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells</p>

“…Natural product xanthones (dibenzo-γ-pyrones) constitutes a significant class of oxygenated heterocycles and occurs as secondary metabolites in microorganisms and plants. 7 This kind of metabolites showed numerous pharmacological activities such as anti-cancer, 8 antioxidant, 9 diuresis and saluresis, 10 hepatoprotective, 11 anti-gout, 12 anti-inflammatory, 13 anti-diabetes, 14 and gastroprotective. 15 Recently, these xanthones easily incorporated into micro-molecules attributing to intriguing biological activities had drew attention from phytochemical, 16 organic synthesis, 17,18 and pharmacological endeavors.…”

Exploration of Novel Xanthine Oxidase Inhibitors Based on 1,6-Dihydropyrimidine-5-Carboxylic Acids by an Integrated in Silico Study

“…The RMSD < 2.0 Å is considered as a reference criterion, indicating that the docking method is reasonable. The same docking method was then applied on 46 ODC XOIs ( Table 1 ), and the appropriate docking conformations with different docking scores were then obtained [ 42 ]. Finally, the conformations of febuxostat, the most active compound 44 , and the least active compound 26 were used for further analyses.…”

Xanthones and Xanthone O‐β‐D‐Glucosides from the Roots of Polygala azizsancarii Dönmez

“…Polygalaceae is one of the few higher plant families rich in xanthones and their O ‐ and C‐glycosidic derivatives that exhibit multiple biological activities, such as cytotoxic, antimicrobial, anti‐inflammatory, antioxidant, and chemotherapeutic effects [19] . Therefore, they were also considered as potential natural compounds for the management of skin inflammatory disorders [20] …”