Mechanistic approach towards interaction of newly synthesized Hesperidin derivatives against xanthine oxidase

Malik, Neelam; Dhiman, Priyanka; Khatkar, Anurag

doi:10.1016/j.ijbiomac.2019.04.017

Cited by 21 publications

(12 citation statements)

References 30 publications

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“…XO was recently emerged as a significant target for gout and hyperuricemia, which is an ideal receptor to characterize the uric acid‐lowering activity of molecular by computational methods (C et al., 2012). Molecular docking simulation revealed that new Hesperidin derivatives interacted with the amino acid residues PHE798, GLN1194, ARG912, THR585, SER1080, and MET1038 positioned inside the binding sites of XO to play their roles (Malik, Dhiman, & Khatkar, 2019). The interaction of the Trp‐Val with the active sites of the XO was better understood via molecular docking with Autodock Vina (Nongonierma, Mooney, Shields, & Fitzgerald, 2013).…”

Section: Resultsmentioning

confidence: 99%

Purification, identification, and computational analysis of xanthine oxidase inhibitory peptides from kidney bean

Hou

2021

Journal of Food Science

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Hyperuricemia is related to plenty of diseases, seriously damaging human health. Current clinical drugs used to treat hyperuricemia have many adverse effects. In this study, kidney bean hydrolysate (KBH) was found to exert high xanthine oxidase inhibitory (XOI) activity. Compared to KBH (50.31 ± 2.73%), XOI activities of three fractions (Mw <5 kDa, Mw<3 kDa, Mw < 1 kDa) by ultrafiltration were higher and increased to 58.58 ± 3.57%, 59.34 ± 1.78%, and 55.05 ± 5.00%, respectively (P < 0.05). A total of 69 peptides were identified by HPLC‐ESI‐MS/MS and analyzed binding affinities with XO with the help of molecular docking. AVDSLVPIGR, DWYDIK, LDNLLR, ISPIPVLK, ISSLEMTR showed well binding affinities with XO and DWYDIK presented the highest XOI activity (68.63 ± 5.07%) among five synthetic peptides (P < 0.05). Additionally, visual analysis results indicated that DWYDIK was pushed into the hydrophobic channel and formed hydrogen bonds with pivotal amino acids of xanthine oxidase. Overall, KBH could be a promising candidate as anti‐ hyperuricemia functional food. Practical Application This research initially revealed that kidney bean peptides could significantly inhibit the activity of xanthine oxidase, indicating kidney bean peptides could be a treatment for hyperuricemia. Kidney bean peptides may have commercial potentials as a safer alternative with few side effects to drugs.

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Section: Resultsmentioning

confidence: 99%

Purification, identification, and computational analysis of xanthine oxidase inhibitory peptides from kidney bean

Hou

2021

Journal of Food Science

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“…Inhibitory potential further increases 10 times when along with nitro, chloro group was also substituted with IC 50 value of 0.263 μM. Molecular docking study suggested that the most potent compound 55 showed hydrogen bond interactions with Arg912, Thr1083, Ser1080 and Gly1260, polar interactions with Gln585, Gln1194, Thr 1077, Ser1080, Thr1083 and Gln1040, hydrophobic interactions with Phe798, Met1038, Tyr592, Leu1042, Val1081, Ala1078, Ala1258 and Val1259, electronegative interactions with Arg912 and Lys1045, and electropositive interaction with Glu1261 (Malik et al, 2019). Maitraie et al synthesized β‐glycyrrhetic acid derivatives and evaluated them for their XO inhibitory potential.…”

Section: Various Synthetic Xo Inhibitorsmentioning

confidence: 99%

Synthetic heterocyclic derivatives as promising xanthine oxidase inhibitors: An overview

et al. 2022

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Inhibition of xanthine oxidase (XO) is an effective and most prominent therapeutic approach for the management of gout. Discovery of its association in the pathophysiology of diabetes, cardiovascular disorders, etc., widened its therapeutic horizons. Limited drug candidates in clinical practice along with side effects forced researchers to develop more efficacious and safer XO inhibitors for the management of gout and other disorders associated with XO hyperactivity. In this regard, this review focus on (a) various drug candidates in clinical practice and under clinical trials, (b) Development of various heterocyclic motifs as XO inhibitors in last two decades and (c) various patented synthetic XO inhibitors.

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“…These studies suggest that flavonoids may have potential applications as XO inhibitors in the treatment of HUA. Molecular simulation revealed that new hesperidin derivatives interacted with the residues Phe798, Gln1194, Arg912, Thr585, Ser1080, and Met1038 positioned inside the binding site of XO . 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 .…”

Section: Introductionmentioning

confidence: 98%

“…Molecular simulation revealed that new hesperidin derivatives interacted with the residues Phe798, Gln1194, Arg912, Thr585, Ser1080, and Met1038 positioned inside the binding site of XO. 10 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. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Wang

Zhang

et al. 2021

ACS Food Sci. Technol.

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Xanthine oxidase (XO) is an important target for the treatment of hyperuricemia (HUA), which mediates the production of uric acid (UA). The mechanism of action between flavonoids and XO in cell biology and structural bioinformatics has not been fully explored. In this study, 160 flavonoids were extensively screened and evaluated for their XO inhibitory activity in vitro. Molecular docking and molecular dynamics (MD) simulation were further used to explore the interaction mechanism between flavonoids and XO. The diosmetin, luteolin, and kaempferol were innovatively found to inhibit the UA production of AML12 cells in a time-and dose-dependent manner, in which the IC 50 is 6.56, 8.92, and 10.46 μM, respectively. Combined with the MD simulations of the complexes of flavonoids and XO, results showed that flavonoids bind the Mo-molybdopterin domain of XO mainly through hydrogen bonding and hydrophobicity. Lys772 and Thr1011 were the key sites to enhance the inhibitory activity of XO.

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Mechanistic approach towards interaction of newly synthesized Hesperidin derivatives against xanthine oxidase

Cited by 21 publications

References 30 publications

Purification, identification, and computational analysis of xanthine oxidase inhibitory peptides from kidney bean

Purification, identification, and computational analysis of xanthine oxidase inhibitory peptides from kidney bean

Synthetic heterocyclic derivatives as promising xanthine oxidase inhibitors: An overview

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

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