The theoretical investigation of monohydroxy flavone: A combined DFT and molecular docking study

Abstract

Gout is caused by hyperuricemia and has become the second largest metabolic disease in China after diabetes mellitus. Because xanthine oxidation (XOD) inhibitors represented by febuxostat, allopurinol, etc. have greater side effects, their clinical application is limited. In addition, the few types of these drugs limit the choice of patients. Previous studies have shown that as a class of potential XOD inhibitors, flavonoids have great development prospects. Because it can not only lower uric acid, but also reduce Reactive Oxygen Species (ROS). The influence of the substitution position and quantity of the hydroxyl group in flavonoids on the structure and properties of such compounds is one of the hotspots in medicinal chemistry research. This structural difference is also reflected in the inhibition of xanthine oxidase. In this study, monohydroxy flavone (MF) were used as a model, using quantum chemical calculations and molecular docking methods to study the structure, properties, antioxidant mechanisms and internal connections of ten compounds. The stability of MFs is improved when a hydroxyl group is introduced at the C5 position, and the substitution at the 2′and C6′ positions will reduce the stability of the compound. When there are hydroxyl groups at positions C5, C3, C6′ and C8, the B ring has a great degree of distortion. The presence of hydroxyl at C3 makes the flavonoids own good antioxidant activity. The hydroxyl group at the C7 position can penetrate deep into the active cavity and combine with the catalytic center, so that the compound can better exert its inhibitory effect. The research results can provide theoretical guidance for the development and upgrade of drugs for the treatment of hyperuricemia and gout.