3,5,2′,4′-Tetrahydroxychalcone, a new non-purine xanthine oxidase inhibitor

被引：43

作者：

Niu, Yanfen ^{[1
]}

Zhu, Huajie ^{[2
]}

Liu, Jia ^{[1
]}

Fan, Huafang ^{[2
,3
]}

Sun, Ling ^{[1
]}

Lu, Wei ^{[1
]}

Liu, Xu ^{[1
]}

Li, Ling ^{[1
]}

机构：

[1] Kunming Med Univ, Yunnan Key Lab Pharmacol Nat Prod, Kunming 650031, Peoples R China

[2] Chinese Acad Sci, Kunming Inst Botany, Organ Synth & Nat Product Lab, State Key Lab Phytochem & Plant Resources W China, Kunming 650204, Peoples R China

[3] Hunan Univ, Coll Chem & Chem Engn, Changsha 410082, Hunan, Peoples R China

来源：

CHEMICO-BIOLOGICAL INTERACTIONS | 2011年 / 189卷 / 03期

关键词：

3,5,2 ',4 '-Tetrahydroxychalcone; Xanthine oxidase; Hyperuricemia; Uric acid; URIC-ACID; HYPERURICEMIA; RAT;

D O I：

10.1016/j.cbi.2010.12.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Xanthine oxidase is a key enzyme that catalyses hypoxanthine and xanthine to uric acid and the overproduction of uric acid will lead to hyperuricemia which is an important cause of gout. In the present study, three chalcone derivatives were synthesized and evaluated for inhibitory activity against xanthine oxidase in vitro. Of the compounds, only Compound 1, 3,5,2',4'-tetrahydroxychalcone, exhibited a significant inhibitory activity on xanthine oxidase with an IC50 value of 22.5 mu M. Lineweaver-Burk transformation of the inhibition kinetics data demonstrated that it was a competitive inhibitor of xanthine oxidase and Ki value was 17.4 mu M. In vivo, intragastric administration of Compound 1 was able to significantly reduce serum uric acid levels and inhibited hepatic xanthine oxidase activities of hyperuricemic mice in a dose-dependent manner. Acute toxicity study in mice showed that Compound 1 was very safe at a dose of up to 5 g/kg. These results suggest that Compound 1 is a novel competitive xanthine oxidase inhibitor and is worthy of further development. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

引用

页码：161 / 166

页数：6

共 26 条

[1]

Amor EC, 2004, Z NATURFORSCH C, V59, P86

[2] Progress towards the discovery of xanthine oxidase inhibitors [J].

Borges, F ;

Fernandes, E ;

Roleira, F .

CURRENT MEDICINAL CHEMISTRY, 2002, 9 (02) :195-217

[3]

CARROLL JJ, 1971, CLIN CHEM, V17, P158

[4]

Edwards N Lawrence, 2008, Cleve Clin J Med, V75 Suppl 5, pS13

[5] Drug-induced Stevens-Johnson syndrome/toxic epidermal necrolysis [J].

Fritsch P.O. ;

Sidoroff A. .

American Journal of Clinical Dermatology, 2000, 1 (6) :349-360

[6] Febuxostat [J].

Hair, Philip I. ;

McCormack, Paul L. ;

Keating, Gillian M. .

DRUGS, 2008, 68 (13) :1865-1874

[7] SUBSTITUTED CYCLIC IMIDES AS POTENTIAL ANTIGOUT AGENTS [J].

HALL, IH ;

SCOVILLE, JP ;

REYNOLDS, DJ ;

SIMLOT, R ;

DUNCAN, P .

LIFE SCIENCES, 1990, 46 (26) :1923-1927

[8] Fatal allopurinol-induced hypersensitivity syndrome in asymptomatic hyperuricaemia [J].

Hammer, B ;

Link, A ;

Wagner, A ;

Böhm, M .

DEUTSCHE MEDIZINISCHE WOCHENSCHRIFT, 2001, 126 (47) :1331-1334

[9] Antioxidative and superoxide scavenging activities of retrochalcones in Glycyrrhiza inflata [J].

Haraguchi, H ;

Ishikawa, H ;

Mizutani, K ;

Tamura, Y ;

Kinoshita, T .

BIOORGANIC & MEDICINAL CHEMISTRY, 1998, 6 (03) :339-347

[10] Allopurinol induces renal toxicity by impairing pyrimidine metabolism in mice [J].

Horiuchi, H ;

Ota, M ;

Nishimura, S ;

Kaneko, H ;

Kasahara, Y ;

Ohta, T ;

Komoriya, K .

LIFE SCIENCES, 2000, 66 (21) :2051-2070

← 1 2 3 →