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Xanthine

About: Xanthine is a research topic. Over the lifetime, 4046 publications have been published within this topic receiving 129820 citations. The topic is also known as: Xanthine.


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Journal ArticleDOI
TL;DR: 1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM) and 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthines was a potent and very A2
Abstract: A series of substituted 8-styryl derivatives of 1,3,7-alkylxanthines was synthesized as potential A2-selective adenosine receptor antagonists, and the potency at rat brain A1- and A2-receptors was studied in radioligand binding experiments. At the xanthine 7-position, only small hydrophobic substituents were tolerated in receptor binding. 7-Methyl analogues were roughly 1 order of magnitude more selective for A2 versus A1 receptors than the corresponding 7-H analogues. 1,3-Dimethylxanthine derivatives tended to be more selective for A2-receptors than the corresponding 1,3-diallyl, diethyl, or dipropyl derivatives. Substitutions of the phenyl ring at the 3-(monosubstituted) and 3,5-(disubstituted) positions were favored. 1,3, 7-Trimethyl-8-(3-chlorostyryl)xanthine was a moderately potent (Ki vs [3H]CGS 21680 was 54 nM) and highly A2-selective (520-fold) adenosine antagonist. 1,3,7-Trimethyl-8-[(3-carboxy-1-oxopropyl)amino] styryl]xanthine was highly A2-selective (250-fold) and of enhanced water solubility (max 19 mM). 1,3-Dipropyl-7-methyl-8-(3,5-dimethoxystyryl) xanthine was a potent (Ki = 24 nM) and very A2-selective (110-fold) adenosine antagonist.

146 citations

Journal ArticleDOI
TL;DR: Co-treatment of the ethanol-exposed NCCs with free radical scavengers including 300 units/ml of superoxide dismutase, catalase, or alpha-tocopherol significantly improved NCC viability and suggest that free radicals play a significant role in ethanol-induced NCC death.
Abstract: Associations between ethanol-induced cranial neural crest cell (NCC) damage in mammalian embryos and subsequent malformations as observed in human fetal alcohol syndrome have previously been illustrated. The vulnerability of NCCs to this teratogen may result, at least in part, from their sensitivity to free radical damage. To examine relationships between free radical generation and NCC cytotoxicity, primary culture of mouse NCCs was used. NCC viability was determined in both dose- and time-response studies involving ethanol exposure. After 48 hr of culture, cell viability was significantly diminished at all doses tested (i.e., 50, 100, 150, and 200 mM ethanol). At 100 mM ethanol (a dosage that is teratogenic in vivo and in whole embryo culture), cell viability decreased to approximately 50% of control values over the first 12 hr of culture, and decreased further, to approximately 20% by 48 hr. Using nitroblue tetrazolium as a probe, it was observed that exposure of NCCs to ethanol stimulated the production of superoxide anion radicals. Co-treatment of the ethanol-exposed NCCs with free radical scavengers including 300 units/ml of superoxide dismutase, catalase (500 units/ml), or alpha-tocopherol (300 microM) significantly improved NCC viability. These results suggest that the ethanol-induced NCC injury is mediated, at least in part, through the generation of free radicals. To test this hypothesis further, NCCs were exposed in culture to xanthine/xanthine oxidase. Exogenous free radicals generated by the xanthine/xanthine oxidase system resulted in reduced NCC viability, the severity of which increased in a time and enzyme concentration-related manner. Superoxide dismutase (300 units/ml) and catalase (500 units/ml) significantly reduced the effects of the xanthine/xanthine oxidase-generated free radicals on NCC viability. The similarity between the susceptibility of NCCs to ethanol and their susceptibility to exogenous free radicals in concert with the free radical scavenger-mediated amelioration of ethanol and exogenous free radical-induced NCC death strongly suggest that free radicals play a significant role in ethanol-induced NCC death.

145 citations

Journal ArticleDOI
TL;DR: 8-Phenyltheophylline was approximately 700 times more potent as antagonist at A1 receptors (bovine brain) than at A2 receptors (human platelets), and PACPX was even 1,600 times more powerful as A1 adenosine receptor antagonist.
Abstract: A variety of alkylxanthines has been comparatively examined as antagonists of A1 adenosine receptors in rat fat cells, rat and bovine cerebral cortex and of A2 adenosine receptors in human platelets. With few exceptions all xanthine derivatives with 7-position substituents such as diprophylline, proxyfylline, pentoxifylline and etofylline were less potent antagonists than xanthine itself which hadK i-values of 170 μmol/l (A1) and 93 μmol/l (A2). Theophylline, caffeine and 3-isobutyl-1-methylxanthine were more potent than xanthine but nearly equipotent antagonists at both receptor subtypes. 8-Phenyl substituents considerably increased the antagonist potency at A1 and A2 receptors. 1,3-Diethyl-8-phenylxanthine was the most potent A2 antagonist (K i 0.2 μmol/l) in human platelets. At A1 receptors 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (PACPX) was the most potent antagonist in all three tissues withK i-values from 0.3 to 8.6 nmol/l. Several 8-phenylxanthine derivatives were remarkably selective antagonists at A1 receptors. 8-Phenyltheophylline was approximately 700 times more potent as antagonist at A1 receptors (bovine brain) than at A2 receptors (human platelets), and PACPX was even 1,600 times more potent as A1 adenosine receptor antagonist. These compounds offer a possibility for a subtype-selective blockade of adenosine receptors.

145 citations

Journal ArticleDOI
TL;DR: Evidence suggests that different forms of membrane damage are responsible for enhanced permeation of the two markers; although glucose-6-P depends on lipid peroxidation, Na+ does not, certainly when EDTA is present.

145 citations

Journal ArticleDOI
TL;DR: The data suggest that inhibition of staurosporine‐induced neuronal apoptosis by preconditioning with xanthine/xanthine oxidase or FeSO4 involves an activation of NF‐κB and an increase in the protein level of Mn‐superoxide dismutase.
Abstract: Preconditioning by a sublethal stimulus induces tolerance to a subsequent, otherwise lethal insult and it has been suggested that reactive oxygen species (ROS) are involved in this phenomenon In the present study, we determined whether preconditioning activates the transcription factor nuclear factor-κB (NF-κB) and how this activation contributes to preconditioning-induced inhibition of neuronal apoptosis Preconditioning was performed by incubating mixed cultures of neurons and astrocytes from neonatal rat hippocampus with xanthine/xanthine oxidase or FeSO4 for 15 min followed by 24 h of recovery which protected the neurons against subsequent staurosporine-induced (200 nm, 24 h) apoptosis The cellular ROS content increased during preconditioning, but returned to basal levels after removal of xanthine/xanthine oxidase or FeSO4 We detected a transient activation of NF-κB 4 h after preconditioning as shown by immunocytochemistry, by a decrease in the protein level of IκBα as well as by electrophoretic mobility shift assay Preconditioning-mediated neuroprotection was abolished by antioxidants, inhibitors of NF-κB activation and cycloheximide suggesting the involvement of ROS, an activation of NF-κB and de novo protein synthesis in preconditioning-mediated rescue pathways Furthermore, preconditioning increased the protein level of Mn-superoxide dismutase which could be blocked by antioxidants, cycloheximide and κB decoy DNA Our data suggest that inhibition of staurosporine-induced neuronal apoptosis by preconditioning with xanthine/xanthine oxidase or FeSO4 involves an activation of NF-κB and an increase in the protein level of Mn-superoxide dismutase

144 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
202361
2022108
202157
202060
201961
201869