Synthesis and bioevaluation of 2-phenyl-5-methyl-2H-1,2,3-triazole-4-carboxylic acid/carbohydrazide derivatives as potent xanthine oxidase inhibitors

RSC Advances ◽  
2016 ◽  
Vol 6 (115) ◽  
pp. 114879-114888 ◽  
Author(s):  
Ailong Shi ◽  
Defa Wang ◽  
He Wang ◽  
Yue Wu ◽  
Haiqiu Tian ◽  
...  
Keyword(s):  
Carboxylic Acid ◽  
Xanthine Oxidase ◽  
Carboxylic Acids ◽  
Inhibitory Activity ◽  
Xanthine Oxidase Inhibitors

A series of 2-phenyl-5-methyl-2H-1,2,3-triazole-4-carboxylic acids/carbohydrazides as analogues of febuxostat were synthesized and evaluated for their in vitro xanthine oxidase (XO) inhibitory activity.

scholarly journals UFLC-MS-IT-TOF and Bioassay Guided Isolation of Flavonoids as Xanthine Oxidase Inhibitors from Diospyros dumetorum

2017 ◽  
Vol 12 (11) ◽  
pp. 1934578X1701201
Author(s):  
Zhen-Tao Deng ◽  
Tong-Hua Yang ◽  
Xiao-Yan Huang ◽  
Xing-Long Chen ◽  
Jian-Gang Zhang ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Folk Medicine ◽  
Hydroxyl Groups ◽  
Active Constituents ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
Pulmonary Abscess ◽  
Xanthine Oxidase Inhibitors

Diospyros dumetorum is an important folk medicine for treating pulmonary abscess and inflammation. The leaves of D. dumetorum revealed xanthine oxidase (XOD) inhibitory activity. With the guidance of UFLC-MS-IT-TOF analyses combined with bioassay in vitro, 15 flavonoids were isolated from the active parts of D. dumetorum. Except for 11 (IC50 > 200μM), all compounds showed obvious XOD inhibitory activity with IC50 values of 32.5 ± 0.7 ~ 145.0 ± 3.3 μM. The preliminary structure-activity relationships study suggested that glycosylation on C-3 was unfavorable for XOD inhibitory activity; hydroxyl groups on ring B were essential for maintaining activity; the activity was closely related with the position of galloylation. This is the first recognition of the XOD inhibitory activity and active constituents of D. dumetorum, and will provide valuable information for this plant as a new resource for treating hyperuricemia and gout.

Synthesis and Biological Evaluation of 5-benzyl-3-pyridyl-1H-1,2,4-triazole Derivatives as Xanthine Oxidase Inhibitors

2020 ◽  
Vol 16 (1) ◽  
pp. 119-127
Author(s):  
Song-Ye Li ◽  
Ting-Jian Zhang ◽  
Qing-Xia Wu ◽  
Kamara M. Olounfeh ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Binding Pocket ◽  
Biological Evaluation ◽  
Triazole Derivatives ◽  
Xanthine Oxidase Inhibitors ◽  
Ic50 Value ◽  
Molecular Modelling Studies ◽  
Modelling Studies

Background: Topiroxostat is an excellent xanthine oxidase (XO) inhibitor, possessing a specific 3,5-diaryl-1,2,4-triazole framework. Objective: The present work was aimed to investigate the preliminary structure-activity relationship (SAR) of 2-cyanopyridine-4-yl-like fragments of topiroxostat analogues. Methods: A series of 5-benzyl-3-pyridyl-1H-1,2,4-triazole derivatives (1a-j and 2a-j) were designed and synthesized by replacement of the 2-cyanopyridine-4-yl moiety with substituted benzyl groups. XO inhibitory activity in vitro was evaluated. Furthermore, molecular modeling simulations were performed to predict the possible interactions between the synthesized compounds and XO binding pocket. Results: The SARs analysis demonstrated that 3,5-diaryl-1,2,4-triazole framework is not essential; in spite of its lower potency, 5-benzyl-3-pyridyl-1H-1,2,4-triazole is an acceptable scaffold for XO inhibitory activity to some extent. A 3′-nitro and a 4′-sec-butoxy group link to the benzyl moiety will be welcome. Furthermore, the most promising compound, 1h, was identified with an IC50 value of 0.16 μM, and the basis of XO inhibition by 1h was rationalized through the aid of molecular modelling studies. Conclusion: Compound 1h could be a lead compound for further investigation and the present work may provide some insight into the search for more structurally diverse XO inhibitors with topiroxostat as a prototype.

scholarly journals Aktivitas Penghambatan Xantin Oksidase pada Ekstrak Daun Sirih Hitam (Piper sp)

2016 ◽  
Vol 3 ◽  
pp. 160-163
Author(s):  
Muhammad Amir Masruhim ◽  
Wisnu Cahyo Prabowo ◽  
Dita Paramitha
Keyword(s):  
Uric Acid ◽  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Ethanol Extract ◽  
Betel Leaf ◽  
Activity Test ◽  
Ic50 Values ◽  
One Way Anova

Hyperuricemia is a condition in which increased levels of uric acid in the blood. Xanthine oxidase role in the oxidation of hypoxanthine and xanthine to uric acid. One treatment of hyperuricemia is inhibiting xanthine oxidase in the process of formation of uric acid. The purpose of this study to determine the inhibitory activity of xanthine oxidase in the ethanol extract of black betel leaf (Piper sp). Xanthine oxidase inhibitory activity test using UV-Vis spectrophotometry in vitro with a concentration of 5 ppm, 10 ppm and 20 ppm. The data obtained were analyzed using one-way ANOVA. The result is the ethanol extract of black betel leaf has a different activity significantly and IC50 values obtained is 65.96 ppm.

Xanthine oxidase inhibitory activity of Euphorbia peplus L. phenolics

2021 ◽  
Vol 24 ◽  
Author(s):  
Emadeldin M. Kamel ◽  
Noha A. Ahmed ◽  
Ashraf A. El-Bassuony ◽  
Omnia E. Hussein ◽  
Barakat Alrashdi ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Active Site ◽  
Inhibitory Activity ◽  
Drug Binding ◽  
Dynamics Simulation ◽  
Solvent Accessible Surface Area ◽  
Radius Of Gyration ◽  
Euphorbia Peplus

Background: Various phenolics show inhibitory activity towards xanthine oxidase (XO), an enzyme that generates reactive oxygen species which cause oxidative damage. Objective: This study investigated the XO inhibitory activity of Euphorbia peplus phenolics. Methods: The dried powdered aerial parts of E. peplus were extracted, fractioned and phenolics were isolated and identified. The XO inhibitory activity of E. peplus extract (EPE) and the isolated phenolics was investigated in vitro and in vivo. Results: Three phenolics were isolated from the ethyl acetate fraction of E. peplus. All isolated compounds and the EPE showed inhibitory activity towards XO in vitro. In hyperuricemic rats, EPE and the isolated phenolics decreased uric acid and XO activity. Molecular docking showed the binding modes of isolated phenolics with XO, depicting significant interactions with the active site amino acid residues. Molecular dynamics simulation trajectories confirmed the interaction of isolated phenolics with XO by forming hydrogen bonds with the active site residues. Also, the root mean square (RMS) deviations of XO and phenolics-XO complexes achieved equilibrium and fluctuated during the 10 ns MD simulations. The radius of gyration and solvent accessible surface area investigations showed that different systems were stabilized at ≈ 2500 ps. The RMS fluctuations profile depicted that the drug binding site exhibited a rigidity behavior during the simulation. Conclusion: In vitro, in vivo and computational investigations showed the XO inhibitory activity of E. peplus phenolics. These phenolics might represent promising candidates for the development of XO inhibitors.

Synthesis and bioevaluation of 2-phenyl-4-methyl-1,3-selenazole-5-carboxylic acids as potent xanthine oxidase inhibitors

2014 ◽  
Vol 85 ◽  
pp. 508-516 ◽  
Author(s):  
Qi Guan ◽  
Zengjin Cheng ◽  
Xiaoxue Ma ◽  
Lijie Wang ◽  
Dongjie Feng ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Carboxylic Acids ◽  
Xanthine Oxidase Inhibitors

Xanthine oxidase inhibitory activity of nicotino/isonicotinohydrazides: A systematic approach from in vitro , in silico to in vivo studies

2017 ◽  
Vol 25 (8) ◽  
pp. 2351-2371 ◽  
Author(s):  
Humaira Zafar ◽  
Muhammad Hayat ◽  
Sumayya Saied ◽  
Momin Khan ◽  
Uzma Salar ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
In Silico ◽  
Systematic Approach ◽  
In Vivo Studies

scholarly journals Identification of a Xanthine Oxidase-inhibitory Component from Sophora Flavescens using NMR-based Metabolomics

2013 ◽  
Vol 8 (10) ◽  
pp. 1934578X1300801
Author(s):  
Ryuichiro Suzuki ◽  
Yuka Hasuike ◽  
Moeka Hirabayashi ◽  
Tatsuo Fukuda ◽  
Yoshihito Okada ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Methanolic Extract ◽  
Sophora Flavescens ◽  
Vitro Assay ◽  
H Nmr ◽  
Plot Analysis ◽  
Inhibitory Compounds ◽  
Loading Plot

We demonstrate that NMR-based metabolomics studies can be used to identify xanthine oxidase-inhibitory compounds in the diethyl ether soluble fraction prepared from a methanolic extract of Sophora flavescens. Loading plot analysis, accompanied by direct comparison of 1H NMR spectra exhibiting characteristic signals, identified compounds exhibiting inhibitory activity. NMR analysis indicated that these characteristic signals were attributed to flavanones such as sophoraflavanone G and kurarinone. Sophoraflavanone G showed inhibitory activity towards xanthine oxidase in an in vitro assay.

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