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.

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.

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 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 Xanthine Oxidase Inhibitory Activity, Chemical Composition, Antioxidant Properties and GC-MS Analysis of Keladi Candik (Alocasia longiloba Miq)

Molecules ◽  
2020 ◽  
Vol 25 (11) ◽  
pp. 2658 ◽  
Author(s):  
Ferid Abdulhafiz ◽  
Arifullah Mohammed ◽  
Fatimah Kayat ◽  
Matcha Bhaskar ◽  
Zulhazman Hamzah ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Side Effects ◽  
Herbal Medicine ◽  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Total Phenolic ◽  
Phytochemical Analysis ◽  
Fruit Extracts ◽  
Ms Analysis ◽  
Ic50 Value

Alocasia longiloba, locally known as ‘Keladi Candik’, has been used traditionally to treat wounds, furuncle and joint inflammations. A. longiloba can be a new source of herbal medicine against hyperuricemia by inhibiting the activity of xanthine oxidase enzyme, the enzyme which is responsible for the development of hyperuricemia in human. Existing xanthine oxidase inhibitors (XOI drugs) show several side effects on gout patients. Therefore, an alternative herbal medicine from plants, with high therapeutic property and free of side effects, are greatly needed. This study was conducted to evaluate XO inhibitory activity, chemical composition, antioxidant activity and GC-MS profile of A. longiloba. Our results showed that ethanolic petiole extract exhibited the highest XO inhibitory activity (70.40 ± 0.05%) with IC50 value of 42.71 μg/mL, followed by ethanolic fruit extracts (61.44 ± 1.24%) with the IC50 value of 51.32 μg/mL. In a parallel study, the phytochemical analysis showed the presence of alkaloid, flavonoid, terpenoids, glycoside and saponin in petiole and fruit extracts, as well as higher total phenolic and flavonoid contents and strong scavenging activity on DPPH and ABTS antioxidant assay. The GC-MS analysis of fruit and petiole extracts revealed the presence of various compounds belonging to different chemical nature, among them are limonen-6-ol, α-DGlucopyranoside, paromomycin, aziridine, phenol, Heptatriacotanol, Phen-1,2,3-dimethyl and Betulin found in ethanolic fruit extract, and Phen-1,4-diol,2,3-dimethyl-, 1-Ethynyl-3,trans(1,1-dimethylethyl), Phenol,2,6-dimethoxy-4-(2-propenyl)- and 7-Methyl-Z-tetradecen-1-olacetate found in ethanolic petiole extract. Some compounds were documented as potent anti-inflammatory and arthritis related diseases by other researchers. In this study, the efficiency of solvents to extract bioactives was found to be ethanol > water, methanol > hexane > chloroform. Together, our results suggest the prospective utilization of fruit and petiole of A. longiloba to inhibit the activity of XO enzyme.

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 Comparative Study of Xanthine Oxidase Inhibitory Activity Of Methanolic Leaf Extracts Of CalophyllumBlancoi (Bitaog), Diospyrospilosanthera (Bolongeta) and SyzygiumCumini (Duhat)

2020 ◽  
Vol 11 (SPL4) ◽  
pp. 531-537
Author(s):  
Jan Asuncion ◽  
Mariane May Domingo ◽  
Rave Harvey Sienna ◽  
ZhaineMarille Villa ◽  
Jennifer Anne Loyola
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Leaf Extract ◽  
Leaf Extracts ◽  
Standard Drug ◽  
Ic50 Value ◽  
Vitro Analysis ◽  
In Vitro Analysis

Gout is characterized as an inflammation and warmth in the joints. It is associated with hyperuricemia wherein an upregulation of xanthine oxidase in purine degradation leads to increased levels of uric acid in the blood. Gout is not fatal. However, it affects one’s quality of life. Thus, this research primarily focuses in determining the inhibitory activity of xanthine oxidase in the methanolic leaf extract of bitaog (Calophyllumblancoi), bolongeta (Diospyrospilosanthera), and duhat (Syzygiumcumini) in gout. A quantitative-experimental research method was used in the study and the data were obtained by measuring the percent inhibition of the samples using UV-Vis spectrophotometer at 290 nm. The results showed that the methanolic leaf extract of above stated plants exhibited exemplary inhibition in comparison with the standard drug, allopurinol. The IC50  value determines the ability of the inhibitor to decrease the biotransformation of a substrate. The principle behind IC50 is, the lower the value the higher the inhibition. The bitaog (Calophyllumblancoi) trials have the lowest IC50 value with an average of 124.3 after the standard drug, followed by bolongeta (Diospyrospilosanthera) have an average of 155.3 IC50 value. Then duhat (Syzygiumcumini) showed the highest IC50 an average of 208.8. The bitaog (Calophyllumblancoi), next to allopurinol, showed the highest inhibition among all the extracts followed by the bolongeta (Diospyrospilosanthera). The least inhibitory activity was observed in duhat (Syzygiumcumini). Hence, it can be concluded that bitaog (Calophyllumblancoi), bolongeta (Diospyrospilosanthera), and duhat (Syzygiumcumini) can inhibit xanthine oxidase using in vitro analysis.

scholarly journals Identification of Novel Thiazolo[5,4-b]Pyridine Derivatives as Potent Phosphoinositide 3-Kinase Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (20) ◽  
pp. 4630
Author(s):  
Liang Xia ◽  
Yan Zhang ◽  
Jingbo Zhang ◽  
Songwen Lin ◽  
Kehui Zhang ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Heterocyclic Compounds ◽  
Kinase Inhibitors ◽  
High Resolution Mass Spectrometry ◽  
Inhibitory Potency ◽  
Docking Analysis ◽  
Ic50 Value ◽  
Phosphoinositide 3 Kinase ◽  
Sar Study ◽  
Potent Inhibitory Activity

A series of novel 2-pyridyl, 4-morpholinyl substituted thiazolo[5,4-b]pyridine analogues have been designed and synthesized in this paper. These thiazolo[5,4-b]pyridines were efficiently prepared in seven steps from commercially available substances in moderate to good yields. All of these N-heterocyclic compounds were characterized by nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) analysis and tested for phosphoinositide 3-kinase (PI3K) enzymatic assay. The results indicated that these N-heterocyclic compounds showed potent PI3K inhibitory activity, and the IC50 of a representative compound (19a) could reach to 3.6 nm. The structure−activity relationships (SAR) study showed that sulfonamide functionality was important for PI3Kα inhibitory activity, and 2-chloro-4-florophenyl sulfonamide (19b), or 5-chlorothiophene-2-sulfonamide (19c) showed potent inhibitory activity with a nanomolar IC50 value. The pyridyl attached to thiazolo[5,4-b]pyridine was another key structural unit for PI3Kα inhibitory potency, and replacement by phenyl lead to a significant decrease in activity. Enzymatic Inhibition results showed that compound 19a inhibited PI3Kα, PI3Kγ, or PI3Kδ with a nanomolar IC50 value, but its inhibitory activity on PI3Kβ was approximately 10-fold reduced. Further docking analysis revealed that the N-heterocyclic core of compound 19a was directly involved in the binding to the kinase through the key hydrogen bonds interaction.

scholarly journals Xanthine Oxidase Inhibitors from Filipendula ulmaria (L.) Maxim. and Their Efficient Detections by HPTLC and HPLC Analyses

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1939
Author(s):  
Maël Gainche ◽  
Clémence Ogeron ◽  
Isabelle Ripoche ◽  
François Senejoux ◽  
Juliette Cholet ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Inhibitory Activity ◽  
Enzyme Inhibitors ◽  
Complex Mixture ◽  
Hplc Method ◽  
Filipendula Ulmaria ◽  
Aerial Parts ◽  
Xanthine Oxidase Inhibitors ◽  
Pure Compounds ◽  
Complementary Strategy

Filipendula ulmaria is a plant commonly used for the treatment of several pathologies, such as diarrhoea, ulcers, pain, stomach aches, fevers, and gout. Our study focused on the use of F. ulmaria for the treatment of gout disease. We first studied the chemical composition of a methanolic extract of the aerial parts and demonstrated its xanthine oxidase (XO) inhibitory activity. Then, we performed a fractionation and evaluated the most XO inhibitory active fractions by UV measurement. Purification of some fractions allowed the determination of the inhibitory activity of pure compounds. We demonstrated that spiraeoside, a glycosylated flavonoid, possesses an activity around 25 times higher than allopurinol, used as a reference in the treatment of gout disease. In order to easily and quickly identify potent inhibitors in complex matrix, we developed a complementary strategy based on an HPLC method and an Effect Directed Assay (EDA) method combining HPTLC and biochemical assays. The HPLC method, capable of determining compounds exhibiting interactions with the enzyme, could be an efficient strategy for evaluating potent enzyme inhibitors in a complex mixture. This strategy could be applied for quantitative assays using LC/MS experiments.

scholarly journals Inhibition Kinetics of Sida rhombifolia L. Extract Toward Xanthine Oxidase by Electrochemical Method

2014 ◽  
Vol 14 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Dyah Iswantini ◽  
Muammar Yulian ◽  
Sri Mulijani ◽  
Trivadila Trivadila
Keyword(s):  
Xanthine Oxidase ◽  
Crude Extract ◽  
Inhibitory Activity ◽  
Electrochemical Method ◽  
Competitive Inhibition ◽  
Ethanol Extract ◽  
Inhibition Kinetics ◽  
Ic50 Value ◽  
Kinetics Of ◽  
Sida Rhombifolia

Sida rhombifolia L. is a traditional medicinal plant that has been known with potential as antigout. The previous research suggested that flavonoids crude extract of S. rhombifolia had an inhibitory activity toward xanthine oxidase by 71% and a spectrophotometric measurement showed that the type of flavonoids crude extract inhibition was a competitive inhibition. The purpose of the research was to investigate the type of inhibition kinetic of S. Rhombifolia’s ethanol extract by electrochemical method and to compare the measurements of linearity and sensitivity between spectrophotometric and electrochemical methods. The results showed that the yield of S. Rhombifolia’s ethanol extract was 9.82% with the inhibitory activity ranging from 13.64% to 82.69% (5.00-200 mg L-1) and IC50 value was 91.15±5.74 mg L-1. Allopurinol as a control showed the inhibitory activity of 15.26-70.95% (0.10-4.00 mg L-1) and IC50 value was 2.45±2.21 mg L-1. Inhibition kinetics of the ethanol extract caused a KM increase and unchange of VMAX. Based on the data, the type of inhibition kinetics was a competitive inhibition, with an inhibitor affinity (α) value of 3.18. Linearity of xanthine oxidase activity assay by electrochemical and spectrophotometric methods showed the range of 0.01-1.00 mM (R2 = 0.978) and 0.05-0.70 mM (R2 = 0.977) respectively. The sensitivity of electrochemical method was reported higher (0.95 μA mM-1) than the spectrophotometric method (0.007 min-1).

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.

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