In Silico and 3D QSAR Studies of Natural Based Derivatives as Xanthine Oxidase Inhibitors

Abstract

<P>Background: A large number of disorders and their symptoms emerge from deficiency or overproduction of specific metabolites has drawn the attention for the discovery of new therapeutic agents for the treatment of disorders. Various approaches such as computational drug design have provided the new methodology for the selection and evaluation of target protein and the lead compound mechanistically. For instance, the overproduction of xanthine oxidase causes the accumulation of uric acid which can prompt gout. </P><P> Objective: In the present study we critically discussed the various techniques such as 3-D QSAR and molecular docking for the study of the natural based xanthine oxidase inhibitors with their mechanistic insight into the interaction of xanthine oxidase and various natural leads. Conclusion: The computational studies of deferent natural compounds were discussed as a result the flavonoids, anthraquinones, xanthones shown the remarkable inhibitory potential for xanthine oxidase inhibition moreover the flavonoids such as hesperidin and rutin were found as promising candidates for further exploration.<P>

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

“…The crystallographic ligand was first redocked into the pocket to examine the dependability of the docking method. The conformation differences between the redocked and original ligands were evaluated by the RMSD values [ 17 ]. The RMSD < 2.0 Å is considered as a reference criterion, indicating that the docking method is reasonable.…”

“…Allopurinol, as a XOI pioneer, was discovered for HUA treatment in the 1960s [ 15 ]. However, allopurinol and its analogues with the semblable purine backbone have been restrained to use in some cases, owing to severe and life-threatening side effects like fever, rashes, kidney toxicity, and Stevens–Johnsons syndrome [ 16 , 17 , 18 ]. Febuxostat and topiroxostat, as novel and effective non-purine XOIs, were approved for marketing in 2009 and 2013, respectively [ 19 , 20 ].…”

Screening and Evaluation of Flavonoids as Xanthine Oxidase Inhibitors for Reducing Uric Acid through Combined Cell Biology and Molecular Simulation

“…11 In addition, Khatkar et al used 3D-QSAR and molecular docking techniques to find that hesperidin and rutin could exert inhibitory activity targeting the XO. 12 Studies indicate that flavonoids may have active pharmacophores targeting XO, and the specific mechanism needs to be further studied.…”

“…A molecular docking study revealed Ser876 and Arg880 as the key amino acids involved in the interaction of the XO with three isoflavonoids from Apios americana . In addition, Khatkar et al used 3D-QSAR and molecular docking techniques to find that hesperidin and rutin could exert inhibitory activity targeting the XO . Studies indicate that flavonoids may have active pharmacophores targeting XO, and the specific mechanism needs to be further studied.…”

Editorial to Special Issue—“Structure-Activity Relationships (SAR) of Natural Products”

“…The topic SAR of NPs is quite broad in scope and could include areas like; bioactive NPs from diverse sources (including those of marine and terrestrial origins) with biological activities exploitable for the treatment of diverse diseases (including infectious diseases and cancer), e.g., mezzettiaside NPs and their disaccharide analogues are known to exhibit both anticancer (H460) and antibacterial (Bacillus subtilis) activities, and their SAR have been previously investigated [8]. Topics that provide insight from binding free energy calculations, docking, pharmacophore modeling, and molecular dynamics involving small molecule NPs and NP mimics are also included [9], along with quantitative structureactivity-relationships (QSAR) applications [10], and may also extend to natural remedies and the pharmacogenomics of age-related and neurodegenerative disorders [11], as well as their the implications in disease-associated epigenetic mechanisms and the chemoinformatic exploration of the chemical space and target space of natural products with epigenetic functions [12]. In terms of applications beyond drug discovery, the role of NPs in environmental remediation could as well be considered [13], as well as the epigenetic mechanisms that lead to the ecological balance between plants, fungi, and microbes, resulting in the biosynthesis of specific kinds of secondary metabolites [14,15].…”