Synthesis and structure–activity relationships of 1-Phenylpyrazoles as xanthine oxidase inhibitors

Ishibuchi, Seigo; Morimoto, Hiroshi; Oe, Takanori; Ikebe, Tsuguo; Inoue, Hirokazu; Fukunari, Atsushi; Kamezawa, Miho; Yamada, Itsunari; Naka, Yoichi

doi:10.1016/s0960-894x(01)00093-2

Cited by 124 publications

(72 citation statements)

References 10 publications

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“…5,6) Briefly, rats were treated with the uricase inhibitor potassium oxonate (PO) (250 mg/kg, i.p.) 1 h before oral (p.o) or intraperitoneal (i.p) administration of test compounds.…”

Section: Methodsmentioning

confidence: 99%

Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats

Nguyen

Awale

Tezuka

et al. 2005

Biological & Pharmaceutical Bulletin

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Gout is a common disease with a worldwide distribution and is mainly caused by deposition of monosodium urate crystals in joints and other tissues as a result of extracellular urate supersaturation.1) This diseases has been associated with hyperuricemia which results from the overproduction and/or underexcretion of uric acid and is greatly influenced by a high dietary intake of nucleic acids. [1][2][3] In the purine metabolism, xanthine and hypoxanthine are oxidized into uric acid by the activity of xanthine oxidase (XO).4) The compounds with ability to enhance the urinary excretion of uric acid or to inhibit uric acid biosynthesis have been generally employed for the treatment of gout.5) Allopurinol, a XO inhibitor which is used in clinically in the treatment of gout, but this drug suffers from many side effects such as hepatitis, nephropathy, and allergic reactions. 6)Chrysanthemum sinense SABINE (Asteraceae) is a medicinal plant which has been used in Vietnamese traditional medicine for the treatment of fever, rheumatism, inflammation, headache, and eyesight disorder. 7) In a previous study, we reported that the methanolic extract of the flowers of this plant and its constituents showed potent inhibitory activity against XO in vitro. 8,9) The results suggested that flavonoids and caffeoylquinic acid derivatives may play an important role in the XO inhibitory activity of this plant. Therefore, in this study we investigated the in vivo hypouricemic effect of acacetin (1) and 4,5-O-dicaffeoylquinic acid methyl ester (2) (Fig. 1), a flavonoid and a caffeoylquinic acid derivative, respectively, included in the flowers of C. sinense, using a rat model of hyperuricemia. MATERIALS AND METHODSChemicals 4,5-O-Dicaffeoylquinic acid methyl ester was isolated from the flowers of C. sinense, and its purity was confirmed by TLC and 1 H-NMR spectral observation as reported previously.10) Acacetin, allopurinol, and uric acid were obtained from Wako Pure Chemicals Industry (Osaka, Japan), and potassium oxonic acid was from Acros Organics (Geel, Belgium). Animals Male Sprague-Dawley rats (6 weeks old, nϭ8) obtained from Sankyo Labo Sevice (Tokyo, Japan) were maintained on a 12-h light/dark cycle in a temperature-and humidity-controlled room for 1 week prior to the experiment. The animals were fed with a laboratory pellet chow (CE-2; CLEA Japan Inc., Tokyo, Japan) and water ad libitum during the experiment. This study was conducted in accordance with the standards established by the Guide for the care and use of Laboratory Animals of Toyama Medical and Pharmaceutical University.Hypouricemic Effect in Potassium Oxonate-Treated Rats An animal model of hyperuricemia induced by the uricase inhibitor potassium oxonate has been used to study in vivo anti-hyperuricemia effects of drugs. 5,6) Briefly, rats were treated with the uricase inhibitor potassium oxonate (PO) (250 mg/kg, i.p.) 1 h before oral (p.o) or intraperitoneal (i.p) administration of test compounds. Blood was taken by cutting the tail tip 2 h after the test drug administ...

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“…5,6) Briefly, rats were treated with the uricase inhibitor potassium oxonate (PO) (250 mg/kg, i.p.) 1 h before oral (p.o) or intraperitoneal (i.p) administration of test compounds.…”

Section: Methodsmentioning

confidence: 99%

Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats

Nguyen

Awale

Tezuka

et al. 2005

Biological & Pharmaceutical Bulletin

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“…The measurement of XO activity was performed in accordance with previously published methods with modifications (40). Briefly, 151.5 µl Tris-HCl buffer (pH 7.5; 100 mM), 7.5 µl XO (0.4 U/m) in 50 mM Tris-HCl buffer (pH 7.5), and 9 µl rosehip extracts [concentrations, 10, 20, 50 and 100 mg/ml (final concentrations, 500, 1,000, 2,500 and 5,000 µg/ml, respectively) in the ethyl acetate extract, and 0.5, 1, 5, 10, 50 mg/ml (final concentrations, 25, 50, 250, 500 and 2,500 µg/ml, respectively) in the hot water and ethanol extracts] were mixed in 1.5-ml tubes.…”

Section: Measurement Of Xo Activity In Vitromentioning

confidence: 99%

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

et al. 2017

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Abstract. Rosehip, the fruit of Rosa canina L., has traditionally been used to treat urate metabolism disorders; however, its effects on such disorders have not been characterized in detail. Therefore, the present study investigated the effects of hot water, ethanol and ethyl acetate extracts of rosehip on xanthine oxidase (XO) activity in vitro. In addition, the serum urate lowering effects of the rosehip hot water extract in a mouse model of hyperuricemia (male ddY mice, which were intraperitoneally injected with potassium oxonate) were investigated. Furthermore, the influence of rosehip hot water extract on CYP3A4 activity, which is the most important drug-metabolizing enzyme from a herb-drug interaction perspective, was investigated. Rosehip extracts of hot water, ethanol and ethyl acetate inhibited XO activity [half maximal inhibitory concentration (IC 50 ) values: 259.6±50.6, 242.5±46.2 and 1,462.8±544.2 µg/ml, respectively]. Furthermore, the administration of 1X rosehip hot water extract significantly reduced the levels of serum urate at 8 h, which was similar when compared with the administration of 1 mg/kg allopurinol. Rosehip hot water extract only marginally affected CYP3A4 activity (IC 50 value, >1 mg/ml). These findings indicate that rosehip hot water extract may present as a functional food for individuals with a high urate level, and as a therapeutic reagent for hyperuricemic patients.

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“…1 Previously reported attempts to try to address these issues include the use of alkynylboronates 9,10 or copper promoters to direct the regioselectivity of the sydnone-alkyne cycloaddition reactions. [11][12][13] Due to the high interest towards new routes to fully functionalised pyrazoles, which are known to possess biological activities, 14,15 we were interested in expanding the scope of the sydnone-alkyne cycloaddition reaction to increase the tolerance for activated and electron-rich alkynes. To do so, we developed the synthesis of 4-aminopyrazoles from cycloaddition reactions between sydnones and ynamides, which have not been reported to date.…”

mentioning

confidence: 99%

Synthesis of aminopyrazoles from sydnones and ynamides

et al. 2017

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Synthesis and structure–activity relationships of 1-Phenylpyrazoles as xanthine oxidase inhibitors

Cited by 124 publications

References 10 publications

Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats

Hypouricemic Effects of Acacetin and 4,5-O-Dicaffeoylquinic Acid Methyl Ester on Serum Uric Acid Levels in Potassium Oxonate-Pretreated Rats

Rosehip inhibits xanthine oxidase activity and reduces serum urate levels in a mouse model of hyperuricemia

Synthesis of aminopyrazoles from sydnones and ynamides

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