Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-...Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)purine (Cyclo-D4G, IMGprodrug) in rat plasma, urine and liver homogenates. Methods Chromatography was performed with C-18Hypersil ODS column and a mobile phase of 7% (v/v) acetonitrile in phosphate buffer, pH 7.40, withUV detection at 283 nm. Results The average extraction recovery of Cyclo-D4G in rat plasma and urinewas 100.1% over its linear range of 0.5 - 80 μg·mL^(-1). The accuracy of the assay was 99.4% .The intra-and inter-day RSDs were less than 9.0% . Conclusion The analytical method was found to beapplicable, reliable and suitable for pharmacokinetic studies.展开更多
（S）-（＋）-2,2-dimethylcyclopropane carbox amide is a key intermediate of Cilastatin, an inhibitor of dehydropeptidase-I. Its corresponding solid-liquid equilibrium data will provide essential support for industrial...（S）-（＋）-2,2-dimethylcyclopropane carbox amide is a key intermediate of Cilastatin, an inhibitor of dehydropeptidase-I. Its corresponding solid-liquid equilibrium data will provide essential support for industrial design and further theoretical studies. The solubilities of （S）-（＋）-2,2-dimethylcyclopropane carbox amide in toluene, dichloromethane, trichloromethane, ethyl acetate, ethanol and pure water at different temperature were measured using the synthetic method by a laser monitoring observation technique. The solubility data were correlated with the modified Apelblat equation.The calculated values were good in agreement with the experimental values.展开更多
Halloysite nanotube-composited thermo-responsive hydrogel system has been successfully developed for controlled drug release by copolymerization of N-isopropylacrylamide （NIPAM） with silane-modified halloysite nanot...Halloysite nanotube-composited thermo-responsive hydrogel system has been successfully developed for controlled drug release by copolymerization of N-isopropylacrylamide （NIPAM） with silane-modified halloysite nanotubes （HNT） through thermally initiated free-radical polymerization. With methylene blue as a model drug, thermo-responsive drug release results demonstrate that the drug release from the nanotubes in the composited hy-drogel can^be well controlled by manipulating the environmental temperature. When the hydrogel network is swol- len at temperature below the lower critical solution temperature （LCST）, drug releases steadily from lumens of the embedded nanotubes, whereas the drug release stops when hydrogel shrinks at temperature above the LCST. The release of model drug from the HNT-composited hydrogel matches well with its thermo-responsive volume phasetransition, and shows characteristics of well controlled release. The design strategy and release results of the pro- posed novel HNT-composited thermo-responsive hydrogel system provide valuable guidance for designing respon- s_i_ve nanocomposites for controlled-release of active agents.展开更多
A highly efficient three-component reaction has been developed for the synthesis of thiazolidinones involving the reaction of 2-amino-l-phenylethanone hydrochloride with an aromatic aldehyde and mercaptoacetic acid in...A highly efficient three-component reaction has been developed for the synthesis of thiazolidinones involving the reaction of 2-amino-l-phenylethanone hydrochloride with an aromatic aldehyde and mercaptoacetic acid in the presence of diisopropylethylamine in a single pot.Critically,this reaction exhibited excellent chemoselectivity,with the nitrogen atom of the 2-amino-l-phenylethanone component reacting selectively with the aromatic aldehyde to give the corresponding Schiff base.Nucleophilic attack at the carbon of the Schiff base by the sulfur atom of mercaptoacetic,followed by a cyclocondensation reaction between the nitrogen and the carboxylic acid moiety afforded the desired thiazolidinones,which were fully characterized by spectroscopic techniques.展开更多
Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major ch...Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.展开更多
文摘Aim To develop a simple and specific high-performance liquid chromatographic(HPLC) method, suitable for the pharmacokinetic studies in vivo, to determine the concentrations of2-amino-6-cyclopropylamino-9-(2,3-dideoxy-β-D-glyceropent-2-enofuranosyl)purine (Cyclo-D4G, IMGprodrug) in rat plasma, urine and liver homogenates. Methods Chromatography was performed with C-18Hypersil ODS column and a mobile phase of 7% (v/v) acetonitrile in phosphate buffer, pH 7.40, withUV detection at 283 nm. Results The average extraction recovery of Cyclo-D4G in rat plasma and urinewas 100.1% over its linear range of 0.5 - 80 μg·mL^(-1). The accuracy of the assay was 99.4% .The intra-and inter-day RSDs were less than 9.0% . Conclusion The analytical method was found to beapplicable, reliable and suitable for pharmacokinetic studies.
文摘（S）-（＋）-2,2-dimethylcyclopropane carbox amide is a key intermediate of Cilastatin, an inhibitor of dehydropeptidase-I. Its corresponding solid-liquid equilibrium data will provide essential support for industrial design and further theoretical studies. The solubilities of （S）-（＋）-2,2-dimethylcyclopropane carbox amide in toluene, dichloromethane, trichloromethane, ethyl acetate, ethanol and pure water at different temperature were measured using the synthetic method by a laser monitoring observation technique. The solubility data were correlated with the modified Apelblat equation.The calculated values were good in agreement with the experimental values.
基金Supported by the National ]qatural Science Foundation of China （20906064）, the National Basic Research Program of China （2009CB623407）, the Program for Changjiang Scholars and Innovative Research Team in University （IRTl163）, and the Foundation for the Author of National Excellent Doctoral Dissertation of China （201163）.
文摘Halloysite nanotube-composited thermo-responsive hydrogel system has been successfully developed for controlled drug release by copolymerization of N-isopropylacrylamide （NIPAM） with silane-modified halloysite nanotubes （HNT） through thermally initiated free-radical polymerization. With methylene blue as a model drug, thermo-responsive drug release results demonstrate that the drug release from the nanotubes in the composited hy-drogel can^be well controlled by manipulating the environmental temperature. When the hydrogel network is swol- len at temperature below the lower critical solution temperature （LCST）, drug releases steadily from lumens of the embedded nanotubes, whereas the drug release stops when hydrogel shrinks at temperature above the LCST. The release of model drug from the HNT-composited hydrogel matches well with its thermo-responsive volume phasetransition, and shows characteristics of well controlled release. The design strategy and release results of the pro- posed novel HNT-composited thermo-responsive hydrogel system provide valuable guidance for designing respon- s_i_ve nanocomposites for controlled-release of active agents.
基金supported by Special Assistance Programme SAP,University Grants Commission,New Delhi,India
文摘A highly efficient three-component reaction has been developed for the synthesis of thiazolidinones involving the reaction of 2-amino-l-phenylethanone hydrochloride with an aromatic aldehyde and mercaptoacetic acid in the presence of diisopropylethylamine in a single pot.Critically,this reaction exhibited excellent chemoselectivity,with the nitrogen atom of the 2-amino-l-phenylethanone component reacting selectively with the aromatic aldehyde to give the corresponding Schiff base.Nucleophilic attack at the carbon of the Schiff base by the sulfur atom of mercaptoacetic,followed by a cyclocondensation reaction between the nitrogen and the carboxylic acid moiety afforded the desired thiazolidinones,which were fully characterized by spectroscopic techniques.
基金Supported by Grants PICT 2008-1521 and 2010-0441,from Agencia Nacional de Promoción Científica y TecnológicaUBACYT CM04,from Universidad de Buenos Aires
文摘Although new research technologies are constantly used to look either for genes or biomarkers in the prediction of metabolic syndrome(MS),the pathogenesis and pathophysiology of this complex disease remains a major challenge.Interestingly,Cheng et al recently investigated possible pathways underlying MS by high-throughput metabolite profiling in two large and well characterized community-based cohorts.The authors explored by liquid chromatography and mass spectrometry the plasma concentrations of 45 distinct metabolites and examined their relation to cardiometabolic risk,and observed that metabolic risk factors such as obesity,insulin resistance(IR),high blood pressure,and dyslipidemia were associated with several metabolites,including branched-chain amino acids,other hydrophobic amino acids,tryptophan breakdown products,and nucleotide metabolites.In addition,the authors found a significant association of IR traits with glutamine,glutamate and the glutamineto-glutamate ratio.These data provide new insight into the pathogenesis of MS-associated phenotypes and introduce a crucial role of glutamine-cycling pathway as prominently involved in the development of metabolic risk.We consider that the hypothesis about the role of abnormal glutamate metabolism in the pathogenesis of the MS is certainly challenging and suggests the critical role of the liver in the global metabolic modulation as glutamate metabolism is linked with aminotransferase reactions.We discuss here the critical role of the "liver metabolism" in the pathogenesis of the MS and IR,and postulate that before fatty liver develops,abnormal levels of liver enzymes,such as alanine and aspartate aminotransferases might reflect high levels of hepatic transamination of amino acids in the liver.
