A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four...A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four bioactive ftavonoids （such as orientin and vitexin） in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C i s column with a mobile phase composed of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITYTM TQD system was operated under the multiple reaction monitoring （MRM） mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations （r 〉 0.99） of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.展开更多
A series of carbamate prodrugs of scutellarin methyl ester （4a-4e） were prepared in the presence of bis（trichloromethyl） carbonate （BTC） with scutellarin methyl esters and L-amino acid tert-butyl ester hydrochlo...A series of carbamate prodrugs of scutellarin methyl ester （4a-4e） were prepared in the presence of bis（trichloromethyl） carbonate （BTC） with scutellarin methyl esters and L-amino acid tert-butyl ester hydrochloride as starting materials. In vitro stability and aqueous solubility of target compounds were evaluated. The results indicated that compounds 4d and 4e have higher solubility and in vitro stability than scutellarin respectively.展开更多
A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in ...A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index （SI） values of 0.48μmol/L and 763.72, respectively.展开更多
基金This work was supported by the National Science Foundation of China （No. 30860366） Guizhou Province Municipal Science and Technology Project （No. 2007-6010）.
文摘A simple and selective ultra performance liquid chromatography--electrospray ionization tandem mass spectrometry （UPLC-ESI-MS/MS） assay was developed for the determination of the human plasma protein binding of four bioactive ftavonoids （such as orientin and vitexin） in Polygonum orientale. Protein precipitation was used for sample preparation. Equilibrium dialysis technique was applied to determine the plasma protein binding under physiological conditions. The separation was achieved through a Waters C i s column with a mobile phase composed of 0.1% formic acid in acetonitrile and 0.1% aqueous formic acid using step gradient elution at a flow rate of 0.35 mL/min. A Waters ACQUITYTM TQD system was operated under the multiple reaction monitoring （MRM） mode of positive electrospray ionization. All of the recovery, precision, accuracy and stability of the method met the requirements. Good correlations （r 〉 0.99） of the four compounds were found, which suggested that these compounds can be simultaneously determined with acceptable accuracy. Results showed that the plasma protein bindings of the four bioactive flavonoids were in the range of 74-89% over the six concentrations studied. The binding parameters containing protein binding affinity, protein binding dissociation constant, and protein binding site were studied. The maximum ability to bind with protein was also determined in the assay in order to understand the drug-protein binding of each compound better.
基金supported by the grants from the National Natural Science Foundation of China(Nos.81260473,81060359)projects of Guizhou Science and Technology Department(Nos. 2012-3013,2010-0519)
文摘A series of carbamate prodrugs of scutellarin methyl ester （4a-4e） were prepared in the presence of bis（trichloromethyl） carbonate （BTC） with scutellarin methyl esters and L-amino acid tert-butyl ester hydrochloride as starting materials. In vitro stability and aqueous solubility of target compounds were evaluated. The results indicated that compounds 4d and 4e have higher solubility and in vitro stability than scutellarin respectively.
基金supported by the National Natural Science Foundation of China(Nos.20962004,81260473)Projects of Guizhou Science and Technology Department(Nos.2013-3031,2012-3013)Excellent Youth Scientific Talents Foundation of Guizhou(No.2013-45)
文摘A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index （SI） values of 0.48μmol/L and 763.72, respectively.
