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In this work, a series of novel compounds Spartinin C1-C24 were screened, synthesised and evaluated for inhibiting xanthine oxidase thus lowering serum uric acid level. The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 μM dosage, which were higher than the positive control Allopurinol. They were low cytotoxic onto human normal hepatocyte cells. Treatment with Spartinin C10 could lower the serum uric acid level to 440.0 μM in the hyperuricemic model mice (723.0 μM), comparable with Allopurinol (325.8 μM). Spartinin C10 was more appreciated than Allopurinol on other serum indexes. The preliminary pharmacokinetics evaluation indicated that the rapid absorption, metabolism and elimination of Spartinin C10 should be further improved. The discovery of pharmaceutical molecules from coastal marine source here might inspire the inter-disciplinary investigations on public health. [ABSTRACT FROM AUTHOR]

The synthesis of 14-(aryl)-14H-naphto[2,1-b]pyrano[3,2-e][1,2,4]triazolo[1,5-c]pyrimidine-2-yl) acetamidoximes2a–ehas been accomplished by reaction of 2-acetonitrile derivatives1a–ewith hydroxylamine. Cyclocondensation reaction of precursors2a–ewith some elctrophilic species such as ethylorthoformate, acetic anhydride, and methyl-acetoacetate provided the new oxadiazole derivatives3a–e,4a–e, and5a–e, respectively. On the other hand, the reaction of precursors2a–ewith 2-chloropropanoyl chloride afforded the new acetimidamides6a–ewhich evolve under reflux of toluene to the new oxadiazoles7a–e. The synthetic compounds were screened for their anti-xanthine oxidase, anti-soybean lipoxygenase, and cytotoxic activities. Moderate to weak xanthine oxidase and soybean lipoxygenase inhibitions were obtained but significant cytotoxic activities were noted. The most cytotoxic activities were recorded mainly (i)5awas the most active (IC50 = 4.0 μM) and selective against MCF-7 and (ii)2awas cytotoxic against the four cell lines with selectivity for MCF-7 and OVCAR-3 (IC50 = 17 and 12 μM, respectively) while2eis highly selective against OVCAR-3 (IC50 = 10 μM). [ABSTRACT FROM PUBLISHER]

From the MeOH extract of the stem of Tetracera scandens L., a new nor-lupane triterpene, 28-O-β-D-glucopyranosyl ester of platanic acid (1), has been isolated together with six known compounds. Their structures were elucidated on the basis of spectroscopic data. Compounds 1–6 displayed significant xanthine oxidase inhibitory activity in a concentration-dependent manner, and compound 4 showed more potent inhibitory activity with an IC50 value of 1.9 µM than that of a positive control allopurinol (IC50 2.5 µM). [ABSTRACT FROM AUTHOR]

Barlerisides A ( 1) and B ( 2), new phenolic glycosides, have been isolated from the n-butanol soluble sub-fraction of Barleria acanthoides along with two known compounds acteoside ( 3) and p-hydroxycinnamic acid ( 4). Their structures have been assigned on the basis of spectral studies. Both 1 and 2 showed significant activity in the superoxide scavenging assay while weak inhibitory activity was observed against the enzyme xanthine oxidase. [ABSTRACT FROM AUTHOR]

A new phenylethanoid glycoside, 2-(3,4-dihydroxyphenyl)-ethyl-O-α-L-rhamnopyranosyl-(1 → 3)-O-α-L-rhamnopyranosyl-(1 → 6)-4-O-E-feruloyl-β-D-glucopyranoside (3-O-methyl poliu-moside, 1) along with five known phenylethanoid glycosides (2-6) were isolated from the aerial parts of Leucas indica Linn. The structure of compound 1 has been elucidated on the basis of spectral data. Compounds 1-6 exhibited significant antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical assay method. These compounds were also found to be moderate inhibitors of xanthine oxidase (XO) enzyme. [ABSTRACT FROM AUTHOR]

In order to evaluate the safety, pharmacological properties, and urate-lowering efficacy of febuxostat, a non-purine, selective inhibitor of xanthine oxidase, a Phase 1, 2-week, multiple-dose, placebo-controlled, dose-escalation study was conducted in 154 healthy adults of both sexes. Daily febuxostat doses in the range 10 mg to 120 mg resulted in proportional mean serum urate reductions ranging from 25% to 70% and in proportional increases in maximum febuxostat plasma concentrations and area under plasma concentration versus time curves. Accompanying the hypouricemic effect were increases in serum xanthine concentrations, decreases in urinary uric acid excretion, and increases in urinary xanthine and hypoxanthine excretion, confirming inhibition of xanthine oxidase activity by febuxostat. Hepatic conjugation and oxidative metabolism were the major pathways of elimination of febuxostat from the body, and renal elimination did not appear to play a significant role. Although not uncommon, adverse events were mild and self-limited, and no deaths or serious adverse events were observed. Febuxostat is a safe and potent hypouricemic agent in healthy humans. [ABSTRACT FROM AUTHOR]

The purpose of this study was the evaluation of the xanthine oxidase (XO) inhibition produced by some synthetic 2-styrylchromones. Ten polyhydroxylated derivatives with several substitution patterns were synthesised, and these and a positive control, allopurinol, were tested for their effects on XO activity by measuring the formation of uric acid from xanthine. The synthesised 2-styrylchromones inhibited xanthine oxidase in a concentration-dependent and non-competitive manner. Some IC 50 values found were as low as 0.55 μM, which, by comparison with the IC 50 found for allopurinol (5.43 μM), indicates promising new inhibitors. Those 2-styrylchromones found to be potent XO inhibitors should be further evaluated as potential agents for the treatment of pathologies related to the enzyme's activity, as is the case of gout, ischaemia/reperfusion damage, hypertension, hepatitis and cancer. [ABSTRACT FROM AUTHOR]