In SilicoDesign and Synthesis of Targeted Curcumin Derivatives as Xanthine Oxidase Inhibitors

2019 ◽  
Vol 20 (5) ◽  
pp. 593-603
Author(s):  
Neelam Malik ◽  
Priyanka Dhiman ◽  
Anurag Khatkar
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Pyrimidine Ring ◽  
Inhibitory Potency ◽  
Curcumin Derivatives ◽  
Xanthine Oxidase Inhibitors ◽  
Excess Production ◽  
Ic50 Values ◽  
Inhibitory Potential ◽  
Potent Inhibitory Activity

Background: Curcumin is a well-known pharmacophore and some of its derivatives are shown to target xanthine oxidase (XO) to alleviate disorders caused by the excess production of uric acid. </p><p> Objective: Curcumin based derivatives were designed, synthesized and evaluated for their antioxidant and xanthine oxidase inhibitory potential. </p><p> Method: In this report, we designed and synthesized two series of curcumin derivatives modified by inserting pyrazole and pyrimidine ring to central keto group. The synthesized compounds were evaluated for their antioxidant and xanthine oxidase inhibitory potential. </p><p> Results: Results showed that pyrazole analogues of curcumin produced excellent XO inhibitory potency with the IC50 values varying from 06.255 &#181;M to 10.503 &#181;M. Among pyrimidine derivatives compound CU3a1 having ortho nitro substitution exhibited more potent xanthine oxidase inhibitory activity than any other curcumin derivative of this series. </p><p> Conclusion: Curcumin derivatives CU5b1, CU5b2, CU5b3, and CU3a1 showed a potent inhibitory activity against xanthine oxidase along with good antioxidant potential.

scholarly journals Phloroglucinol Derivatives from Dryopteris crassirhizoma as Potent Xanthine Oxidase Inhibitors

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 122
Author(s):  
Heung Joo Yuk ◽  
Ji-Yul Kim ◽  
Yoon-Young Sung ◽  
Dong-Seon Kim
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Etoac Extract ◽  
Xanthine Oxidase Inhibitors ◽  
Ic50 Value ◽  
Phloroglucinol Derivatives ◽  
Acetyl Group ◽  
Potent Inhibitory Activity ◽  
Better Than ◽  
Comparative Activity

Dryopteris crassirhizoma rhizomes are used as a traditional medicine in Asia. The EtOAc extract of these roots has shown potent xanthine oxidase (XO) inhibitory activity. However, the main phloroglucinols in D. crassirhizoma rhizomes have not been analyzed. Thus, we investigated the major constituents responsible for this effect. Bioassay-guided purification isolated four compounds: flavaspidic acid AP (1), flavaspidic acid AB (2), flavaspidic acid PB (3), and flavaspidic acid BB (4). Among these, 1 showed the most potent inhibitory activity with a half-maximal inhibitory concentration (IC50) value of 6.3 µM, similar to that of allopurinol (IC50 = 5.7 µM) and better than that of oxypurinol (IC50 = 43.1 µM), which are XO inhibitors. A comparative activity screen indicated that the acetyl group at C3 and C3′ is crucial for XO inhibition. For example, 1 showed nearly 4-fold higher efficacy than 4 (IC50 = 20.9 µM). Representative inhibitors (1–4) in the rhizomes of D. crassirhizoma showed reversible and noncompetitive inhibition toward XO. Furthermore, the potent inhibitors were shown to be present in high quantities in the rhizomes by a UPLC-QTOF-MS analysis. Therefore, the rhizomes of D. crassirhizoma could be used to develop nutraceuticals and medicines for the treatment of gout.

scholarly journals Assessment of antioxidant and xanthine oxidase inhibitory activity of Triadica cochinchinensis stem bark

2019 ◽  
Vol 1 (1) ◽  
pp. 39-44
Author(s):  
Carla Wulandari Sabandar ◽  
◽  
Juriyati Jalil ◽  
Norizan Ahmat ◽  
Nor-Ashila Aladdin ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Methanol Extract ◽  
Radical Scavenging ◽  
Stem Bark ◽  
Total Phenolic ◽  
Xanthine Oxidase Inhibitors ◽  
Ic50 Values ◽  
Organic Fractions ◽  
Promising Source

Triadica cochinchinensis has been used traditionally to treat diseases related to oxidative stress. Nonetheless, little is known about its biological activity. This study aimed to evaluate the antioxidant and xanthine oxidase inhibitory activity of this plant. For this purpose, qualitative phytochemicals, total phenolic, total flavonoid, antioxidant assays (DPPH and FRAP), and xanthine oxidase assay were evaluated towards methanol and organic fractions of its stem bark. Results showed the occurrence of flavonoids, tannins, terpenoids, steroids, and saponins in the methanol extract. The extract and its two fractions (ethyl acetate and methanol) exhibited promising radical scavenging (IC50 values between 3.6-4.5 μg/mL) and ferric reduction activities (4.2-5.5 μg/μg of equivalent trolox amount). They also exhibited inhibition on the xanthine oxidase activity ranging from 43.8 to 80.5% at a dose of 100 μg/mL. These activities could be attributed to the amount of phenolics in the methanol extract and active fractions (136.6-174.1 mg GAE/g of sample). Our results suggested that the methanol extract of T. cochinchinensis stem bark could be used as a promising source of lead molecules for antioxidant and xanthine oxidase inhibitors from natural source.

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.

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.

scholarly journals EVALUATION OF XANTHINE OXIDASE INHIBITORY ACTIVITY BY FLAVONOIDS FROM PONGAMIA PINNATA LINN

2017 ◽  
Vol 10 (3) ◽  
pp. 360 ◽  
Author(s):  
Vanishree Bambrana ◽  
Dayanand Cd ◽  
Sheela Sr
Keyword(s):  
Xanthine Oxidase ◽  
Plant Extracts ◽  
Inhibitory Activity ◽  
Mangifera Indica ◽  
Zingiber Officinale ◽  
Pongamia Pinnata ◽  
Morinda Citrifolia ◽  
Dried Fruit ◽  
Fruit Powder ◽  
Inhibitory Potential

ABSTRACTObjective: Flavonoids from the crude seeds extract of Pongamia pinnata L., dried fruit powder of Morinda citrifolia L., bark of Mangifera indica L., andrhizome of Zingiber officinale Rosc. were screened for xanthine oxidase (XO) inhibition at different concentration. The inhibitory potential of quercetinand allopurinol were used for the determination of 50% inhibitory concentration (IC50) and Ki values.Methods: Isolation of flavonoids from the plant extracts was processed by column chromatography and tested for XO inhibitory activity in the rangeof 6-800 μg/ml.Results: The results demonstrated that optimized flavonoids extract of P. pinnata L. exhibited promising XO inhibition. P. pinnata L., M. indica L., andZ. officinale Rosc. had IC50 in the concentration of 8.74 mM, 1.09 mM, 5.4 mM and Ki 0.35 mM, 1.73 mM, 2.7 mM, respectively.Conclusion: The study showed that plant species under investigation exhibited XO inhibition by optimized flavonoid extract. P. pinnata L. indicatedpromising XO inhibition compared to other plant extracts. Flavonoids can be used as a potent inhibitor of XO an alternative to allopurinol.Keywords: Xanthine oxidase, Quercetin, Allopurinol, Pongamia pinnata, Oxidative stress.

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 5-Substituted N-(9H-purin-6-yl)-1,2-oxazole-3-carboxamides as xanthine oxidase inhibitors

2020 ◽  
Vol 15 (1) ◽  
pp. 20-25
Author(s):  
Oksana Muzychka ◽  
Olexandr Kobzar ◽  
Oleg Shablykin ◽  
Volodymyr Brovarets ◽  
Andriy Vovk
Keyword(s):  
Xanthine Oxidase ◽  
Inhibition Efficiency ◽  
Enzyme Inhibitor ◽  
Oxazole Ring ◽  
Inhibitor Complex ◽  
Enzyme Substrate ◽  
Xanthine Oxidase Inhibitors ◽  
Ic50 Values ◽  
Nanomolar Range

Synthetic 6-substituted purine derivatives are known to exhibit diverse bioactivity. In this paper, a series of N-(9H-purin-6-yl)-1,2-oxazole-3-carboxamide derivatives were synthesized and evaluated in vitro against xanthine oxidase, an enzyme of purine catabolism. The introduction of aryl substituent at position 5 of the oxazole ring was found to increase the inhibition efficiency. Some of the inhibitors containing 5-substituted isoxazole and purine moieties were characterized by IC50 values in the nanomolar range. According to the kinetic data, the most active N-(9H-purin-6-yl)-5-(5,6,7,8-tetrahydronaphthalen-2-yl)-1,2-oxazole-3-carboxamide demonstrated a competitive type of inhibition with respect to the enzyme-substrate. Molecular docking was carried out to elucidate the mechanism of enzyme-inhibitor complex formation. The data obtained indicate that xanthine oxidase may be one of the possible targets for the bioactive purine carboxamides.

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

2019 ◽  
Vol 19 (2) ◽  
pp. 123-138 ◽  
Author(s):  
Neelam Malik ◽  
Priyanka Dhiman ◽  
Anurag Khatkar
Keyword(s):  
Xanthine Oxidase ◽  
3D Qsar ◽  
Computational Drug Design ◽  
Qsar Studies ◽  
Mechanistic Insight ◽  
Xanthine Oxidase Inhibitors ◽  
Oxidase Inhibition ◽  
Xanthine Oxidase Inhibition ◽  
Inhibitory Potential ◽  
Insight Into

<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>

scholarly journals Inhibition of Soybean 15-Lipoxygenase by Naturally Occurring Acetophenones and Derricidin

2015 ◽  
Vol 10 (4) ◽  
pp. 1934578X1501000
Author(s):  
Vito Alessandro Taddeo ◽  
Francesco Epifano ◽  
Salvatore Genovese ◽  
Serena Fiorito
Keyword(s):  
Secondary Metabolites ◽  
Inhibitory Activity ◽  
Inhibitory Potency ◽  
Naturally Occurring ◽  
Potent Inhibitory Activity

Three selected naturally occurring oxyprenylated secondary metabolites, namely 2-hydroxy4-isopentenyloxyacetophenone (1), 4-geranyloxy-2-hydroxyacetophenone (2), 4-farnesyloxyacetophenone (3), and derricidin (4) were synthesized and their inhibitory potency against soybean 15-lipoxygenase evaluated. Compounds 1 and 4 showed the most potent inhibitory activity with IC50 values of 2.5 μM and 0.6 μM.

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.

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