In silico design and synthesis of targeted rutin derivatives as xanthine oxidase inhibitors

Abstract

Background Xanthine oxidase is an important enzyme of purine catabolism pathway and has been associated directly in pathogenesis of gout and indirectly in many pathological conditions like cancer, diabetes and metabolic syndrome. In this research rutin, a bioactive flavonoid was explored to determine the capability of itself and its derivatives to inhibit xanthine oxidase. Objective To develop new xanthine oxidase inhibitors from natural constituents along with antioxidant potential. Method In this report, we designed and synthesized rutin derivatives hybridized with hydrazines to form hydrazides and natural acids to form ester linkage with the help of molecular docking. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. Results The enzyme kinetic studies performed on rutin derivatives showed a potential inhibitory effect on XO ability in competitive manner with IC 50 value ranging from 04.708 to 19.377 µM and RU3a 3 was revealed as most active derivative. Molecular simulation revealed that new rutin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, GLN 767, ALA1078 and MET1038 positioned inside the binding site of XO. Results of antioxidant activity revealed that all the derivatives showed very good antioxidant potential. Conclusion Taking advantage of molecular docking, this hybridization of two natural constituent could lead to desirable xanthine oxidase inhibitors with improved activity. Electronic supplementary material The online version of this article (10.1186/s13065-019-0585-8) contains supplementary material, which is available to authorized users.

Identification of phenolics from miracle berry (Synsepalum dulcificum) leaf extract and its antiangiogenesis and anticancer activities

“…But the expression of inosine, hypoxanthine and xanthine was higher in MBL extract treated groups than that in the NT group. Some studies reported that gallic acid ( 47 ) and rutin ( 48 ) could inhibits xanthine oxidase, which was consistent with our results. The inhibitory effect of these components in the MBL extract on xanthine oxidase may also be related to their antitumor effect ( 49 ).…”

Advances in structures required of polyphenols for xanthine oxidase inhibition

“…Besides, the hydrazine‐ and aniline‐substituted derivatives of rutin, especially Rua 3 (Figure 2), also showed remarkable inhibitions on XO even much stronger than allopurinol did (IC 50 value is only half of that of allopurinol). The two aniline derivatives of rutin also showed XO inhibitory effects as potent as allopurinol did (Malik, Dhiman, & Khatkar, 2019).…”

Therapeutic benefits of rutin and its nanoformulations

“…Besides, rutin is synthesized through a series of enzymatic modifications (Li et al, 2014). Several methods are suggested for rutin and rutin derivatives extraction from various plants, including heat reflux extraction, ultrasound‐assisted extraction, mechanochemical assisted extraction, solid phase micro‐extraction, supercritical fluid extraction, infrared assisted extraction, microwave‐assisted extraction, and pressurized liquid extraction (Malik, Dhiman, & Khatkar, 2019).…”