2013 Vol. 44 No. 3
2013, 44(3): 193-201.
DOI: 10.11665/j.issn.1000-5048.20130301
Abstract：
In the past decade, thousands of chiral organocatalysts have emerged for asymmetric synthesis, and opened up new channels and shortcuts, especially in the synthesis of chiral drug intermediates. They play an important role in developing new methods for the synthesis of new drugs. In these review, chiral organocatalytic reactions are summarized and classified based on the interaction manner way between chiral organocayalysts and substrates. The latest developments of organocatalysis and their applications in drug synthesis are present hereinafter for exploring and developing better organocatalysis.
In the past decade, thousands of chiral organocatalysts have emerged for asymmetric synthesis, and opened up new channels and shortcuts, especially in the synthesis of chiral drug intermediates. They play an important role in developing new methods for the synthesis of new drugs. In these review, chiral organocatalytic reactions are summarized and classified based on the interaction manner way between chiral organocayalysts and substrates. The latest developments of organocatalysis and their applications in drug synthesis are present hereinafter for exploring and developing better organocatalysis.
Abstract：
A series of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids( 8a - 8i) were synthesized, and their structures were confirmed by 1H NMR and MS. The inhibitory activity of the target compounds against adenosine diphosphate(ADP)-induced platelet aggregation was evaluated in vitro by Born′s turbidimetric assay. In comparison with 3-n-butylphthalide(NBP), compound 8i possessed better antiplatelet aggregation activity and aqueous solubility. Therefore, compound 8i may be a potential platelet aggregation inhibitor for further investigation.
A series of carbamate-isosorbide-3-n-butylphthalide ring opening derivative trihybrids( 8a - 8i) were synthesized, and their structures were confirmed by 1H NMR and MS. The inhibitory activity of the target compounds against adenosine diphosphate(ADP)-induced platelet aggregation was evaluated in vitro by Born′s turbidimetric assay. In comparison with 3-n-butylphthalide(NBP), compound 8i possessed better antiplatelet aggregation activity and aqueous solubility. Therefore, compound 8i may be a potential platelet aggregation inhibitor for further investigation.
2013, 44(3): 207-209.
DOI: 10.11665/j.issn.1000-5048.20130303
Abstract：
Eight compounds were isolated from the tuber of Curcuma longa, and identified as curcumin( 1 ), demethoxycurcumin( 2 ), bisdemethoxycurcumin( 3 ), 4-hydroxybenzaldehyde( 4 ), vanillin( 5 ), 4-(4-hydroxyphenyl)butan-2-one( 6 ), (+)-rhododendrol( 7 ), and(2R, 4R)-6-(4′-hydroxyphenyl)-hexane-2, 4-diol( 8 ). Among them, compounds 4 - 7 were isolated from this plant for the first time, and compound 8 was a novel compound.
Eight compounds were isolated from the tuber of Curcuma longa, and identified as curcumin( 1 ), demethoxycurcumin( 2 ), bisdemethoxycurcumin( 3 ), 4-hydroxybenzaldehyde( 4 ), vanillin( 5 ), 4-(4-hydroxyphenyl)butan-2-one( 6 ), (+)-rhododendrol( 7 ), and(2R, 4R)-6-(4′-hydroxyphenyl)-hexane-2, 4-diol( 8 ). Among them, compounds 4 - 7 were isolated from this plant for the first time, and compound 8 was a novel compound.
2013, 44(3): 210-212.
DOI: 10.11665/j.issn.1000-5048.20130304
Abstract：
Seven compounds were isolated from the bark of Platanus acerifolia Wild. , and identified as betulinic acid( 1 ), platanic acid( 2 ), β-sistosterol( 3 ), 3-O-acetylbetulin aldehyde( 4 ), 3-O-acetyl oleanolic acid( 5 ), 4′, 5, 7-trihydroxy-8-prenylflavone( 6 )and platanone B( 7 ). Compound 6 was isolated from this genus for the first time; compounds 2 - 5 were isolated from this plant for the first time; and compound 7 was a novel natural product.
Seven compounds were isolated from the bark of Platanus acerifolia Wild. , and identified as betulinic acid( 1 ), platanic acid( 2 ), β-sistosterol( 3 ), 3-O-acetylbetulin aldehyde( 4 ), 3-O-acetyl oleanolic acid( 5 ), 4′, 5, 7-trihydroxy-8-prenylflavone( 6 )and platanone B( 7 ). Compound 6 was isolated from this genus for the first time; compounds 2 - 5 were isolated from this plant for the first time; and compound 7 was a novel natural product.
2013, 44(3): 213-218.
DOI: 10.11665/j.issn.1000-5048.20130305
Abstract：
Fourteen compounds were isolated and purified from ethyl acetate extract of Cynanchum otophyllum Schneid. , and were identified as otophylloside A( 1 ), otophylloside B( 2 ), 2, 5-dihydroxyacetophenone( 3 ), methyl 2, 5-dihydroxy-benzoate( 4 ), vanillin( 5 ), arjunolic acid( 6 ), glycosmisic acid( 7 ), caudatin-3-O-β-D- cymaropyranosyl-(1→4)-β-D-oleandropyranosl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 8 ), penupogenin( 9 ), caudatin-3-O-β-D-glucopyranosyl-(1 →4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 10 ), qingyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D- cymaropyranosyl-(1→4)-β-D-digitoxopyranoside( 11 ), and kidjoranin-3-O-β-D- cymaropyranoside( 12 ), qingyangshengenin-3-O-β-D-cymaropyranosyl-(1→4)-β-D- digitoxopyranoside( 13 ), and kidjoranin-3-O-β-D-oleandropyranosyl-(1→4)-β-D- cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 14 )by physicochemical properties and spectroscopic analyses. Among them, compounds 6-7 were firstly isolated from the genus Cynanchum, and compounds 3-5, 8-14 were isolated from this plant for the first time.
Fourteen compounds were isolated and purified from ethyl acetate extract of Cynanchum otophyllum Schneid. , and were identified as otophylloside A( 1 ), otophylloside B( 2 ), 2, 5-dihydroxyacetophenone( 3 ), methyl 2, 5-dihydroxy-benzoate( 4 ), vanillin( 5 ), arjunolic acid( 6 ), glycosmisic acid( 7 ), caudatin-3-O-β-D- cymaropyranosyl-(1→4)-β-D-oleandropyranosl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 8 ), penupogenin( 9 ), caudatin-3-O-β-D-glucopyranosyl-(1 →4)-β-D-oleandropyranosyl-(1→4)-β-D-cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 10 ), qingyangshengenin-3-O-β-D-oleandropyranosyl-(1→4)-β-D- cymaropyranosyl-(1→4)-β-D-digitoxopyranoside( 11 ), and kidjoranin-3-O-β-D- cymaropyranoside( 12 ), qingyangshengenin-3-O-β-D-cymaropyranosyl-(1→4)-β-D- digitoxopyranoside( 13 ), and kidjoranin-3-O-β-D-oleandropyranosyl-(1→4)-β-D- cymaropyranosyl-(1→4)-β-D-cymaropyranoside( 14 )by physicochemical properties and spectroscopic analyses. Among them, compounds 6-7 were firstly isolated from the genus Cynanchum, and compounds 3-5, 8-14 were isolated from this plant for the first time.
2013, 44(3): 219-222.
DOI: 10.11665/j.issn.1000-5048.20130306
Abstract：
To study the dynamic behavior of matrix metalloproteinases(MMPs)S′1 binding pocket, and the structural properties relevant for the design of specific inhibitors at the molecular level, long-time molecular dynamics simulation of apo proteases of MMP-7, MMP-2 and MMP-3 were performed. It was found that the S′1 binding pocket of MMP-7 and MMP-2 was closed, while S′1 binding pocket of MMP-3 was semi-closed. Thus, the flexibility of S′1 binding pocket loop region may play an important role in binding inhibitors.
To study the dynamic behavior of matrix metalloproteinases(MMPs)S′1 binding pocket, and the structural properties relevant for the design of specific inhibitors at the molecular level, long-time molecular dynamics simulation of apo proteases of MMP-7, MMP-2 and MMP-3 were performed. It was found that the S′1 binding pocket of MMP-7 and MMP-2 was closed, while S′1 binding pocket of MMP-3 was semi-closed. Thus, the flexibility of S′1 binding pocket loop region may play an important role in binding inhibitors.
2013, 44(3): 223-227.
DOI: 10.11665/j.issn.1000-5048.20130307
Abstract：
To study the three-dimensional quantitative-structure activity relationship(3D-QSAR)of 39 dimorpholino derivatives as phosphatidylinositol-3-kinases α(PI3Kα)inhibitors, a self-organizing molecular field analysis(SOMFA)model has been established. The cross-validated correlation coefficient(q2), non-cross-validated correlation coefficient(r2)and standard error of estimate(SEE)reached 0. 636, 0. 702 and 0. 581, respectively. The contribution coefficient of the shape and electrostatic potential reached 0. 7 and 0. 3, respectively. This model was validated by a group of compounds as test set. The predicted non-cross-validated correlation coefficient(r2pred)reached 0. 808. With its obvious statistical significance, this model may provide a way to develop novel dimorpholino derivatives as PI3Kα inhibitors.
To study the three-dimensional quantitative-structure activity relationship(3D-QSAR)of 39 dimorpholino derivatives as phosphatidylinositol-3-kinases α(PI3Kα)inhibitors, a self-organizing molecular field analysis(SOMFA)model has been established. The cross-validated correlation coefficient(q2), non-cross-validated correlation coefficient(r2)and standard error of estimate(SEE)reached 0. 636, 0. 702 and 0. 581, respectively. The contribution coefficient of the shape and electrostatic potential reached 0. 7 and 0. 3, respectively. This model was validated by a group of compounds as test set. The predicted non-cross-validated correlation coefficient(r2pred)reached 0. 808. With its obvious statistical significance, this model may provide a way to develop novel dimorpholino derivatives as PI3Kα inhibitors.
2013, 44(3): 228-233.
DOI: 10.11665/j.issn.1000-5048.20130308
Abstract：
The aim of the research was to prepare paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate grafted with c(RGDyK)(PTX-LHRyK)nanoparticles, and to study the in vivo and in vitro anti-tumor effect of the PTX-LHRyK nanoparticles. The PTX-LHRyK nanoparticles were prepared by dialysis and characterized in terms of size, Zeta potential, and drug entrapment efficiency. The effect of PTX-LHRyK nanoparticles on PTX-induced cytotoxicity was investigated in B16F10 cell lines by MTT assay. The in vivo anti-tumor effect(in terms of tumor growth)and tumor inhibition rate were also evaluated. The PTX-LHRyK nanoparticles were generally spherical with a mean diameter of(131. 7±2. 3)nm, a negative surface charge, and encapsulation efficiency of(84. 84±2. 63)%. The tumor inhibition rate of the PTX-LHRyK nanoparticles was up to 75. 28%, which is 1. 46-fold higher than the combined injection. It was shown in the in vitro anti-tumor activity study that the PTX-LHRyK nanoparticles displayed slightly higher in vitro cytotoxicity as compared to the combined injection as the increase of the incubate time, but LHRyK conjugate at the studied concentration range did not show significant influence on the cell viability of the B16F10 cells。The in vivo anti-tumor effect of the PTX was significantly improved using the LHRyK conjugate as a carrier, with more powerful anti-tumor activity than PTX-ATRA-INJ as well as lower side-effects.
The aim of the research was to prepare paclitaxel-loaded low molecular weight heparin-all-trans-retinoid acid conjugate grafted with c(RGDyK)(PTX-LHRyK)nanoparticles, and to study the in vivo and in vitro anti-tumor effect of the PTX-LHRyK nanoparticles. The PTX-LHRyK nanoparticles were prepared by dialysis and characterized in terms of size, Zeta potential, and drug entrapment efficiency. The effect of PTX-LHRyK nanoparticles on PTX-induced cytotoxicity was investigated in B16F10 cell lines by MTT assay. The in vivo anti-tumor effect(in terms of tumor growth)and tumor inhibition rate were also evaluated. The PTX-LHRyK nanoparticles were generally spherical with a mean diameter of(131. 7±2. 3)nm, a negative surface charge, and encapsulation efficiency of(84. 84±2. 63)%. The tumor inhibition rate of the PTX-LHRyK nanoparticles was up to 75. 28%, which is 1. 46-fold higher than the combined injection. It was shown in the in vitro anti-tumor activity study that the PTX-LHRyK nanoparticles displayed slightly higher in vitro cytotoxicity as compared to the combined injection as the increase of the incubate time, but LHRyK conjugate at the studied concentration range did not show significant influence on the cell viability of the B16F10 cells。The in vivo anti-tumor effect of the PTX was significantly improved using the LHRyK conjugate as a carrier, with more powerful anti-tumor activity than PTX-ATRA-INJ as well as lower side-effects.
2013, 44(3): 234-238.
DOI: 10.11665/j.issn.1000-5048.20130309
Abstract：
Lyophilized temsirolimus-loaded liposomes were prepared; the formulations were optimized; and the pharmacokinetics in rats was investigated. The lyophilized temsirolimus-loaded liposomes were prepared by film dispersion, followed by freeze drying. Formulations were optimized by single-factor design. The optimized formulation contained 24 mg/mL phosphatidyl choline(PC), a weight ratio of 1 ∶40 between drug loading and PC, and a weight ratio of 10 ∶1 between PC and cholersterol. Sucrose was determined as an optimal lyoprotectant, and the weight ratio between sucrose and PC was 2 ∶1. The optimized liposomes had a particle size of(100. 8±6. 74)nm and an entrapment efficiency of(95. 24±3. 58)%. Dialytic method was used to investigate the drug release profile. Less than 30% of entrapped drug was released after 24 h at pH 7. 4 under 37 °C. In addition, pharmacokinetics of temsirolimus in rats receiving commercial product Torisel® and temsirolimus-loaded liposomes was evaluated after HPLC determination of temsirolimus in rat plasma. cmax and AUC of the liposomes were 2. 06- and 1. 49-fold improved relative to that of Torisel® , respectively. In conclusion, the optimized lyophilized temsirolimus-loaded liposomes with high entrapment efficiency achieved sustained release and significantly increased bioavailability of temsirolimus in rats.
Lyophilized temsirolimus-loaded liposomes were prepared; the formulations were optimized; and the pharmacokinetics in rats was investigated. The lyophilized temsirolimus-loaded liposomes were prepared by film dispersion, followed by freeze drying. Formulations were optimized by single-factor design. The optimized formulation contained 24 mg/mL phosphatidyl choline(PC), a weight ratio of 1 ∶40 between drug loading and PC, and a weight ratio of 10 ∶1 between PC and cholersterol. Sucrose was determined as an optimal lyoprotectant, and the weight ratio between sucrose and PC was 2 ∶1. The optimized liposomes had a particle size of(100. 8±6. 74)nm and an entrapment efficiency of(95. 24±3. 58)%. Dialytic method was used to investigate the drug release profile. Less than 30% of entrapped drug was released after 24 h at pH 7. 4 under 37 °C. In addition, pharmacokinetics of temsirolimus in rats receiving commercial product Torisel® and temsirolimus-loaded liposomes was evaluated after HPLC determination of temsirolimus in rat plasma. cmax and AUC of the liposomes were 2. 06- and 1. 49-fold improved relative to that of Torisel® , respectively. In conclusion, the optimized lyophilized temsirolimus-loaded liposomes with high entrapment efficiency achieved sustained release and significantly increased bioavailability of temsirolimus in rats.
2013, 44(3): 239-243.
DOI: 10.11665/j.issn.1000-5048.20130310
Abstract：
Cyclosporine A-loaded human serum albumin nanoparicles(CyA-HSA)were prepared and physicochemical properties including entrapment efficiency, drug-loading capability, particles size, Zeta potential, morphology, pH value and osmotic pressure were evaluated. Dialysis was undertaken to investigate the release of CyA from CyA-HSA nanoparticles in vitro. The obtained CyA-HSA nanoparticles showed spherical shape with mean particle sizes of 240. 5 nm and Zeta potential of -32. 0 mV. The drug-loading amount and entrapment efficiency were 14. 7% and 85. 8%, respectively. The pH and osmotic pressure of nanoparticles were 7. 0 and 314. 7 mOsmol/kg, respectively. CyA-HSA nanoparticles exhibited better dilution stability than commercial cyclosporine A injection, Sandimmune® . Both CyA-HSA and Sandimmune® exhibited significant sustained release behavior in vitro and both release profiles displayed a zero-order process. The pharmacokinetic study at equal administration dosage(7 mg/kg)in rats showed that cyclosporine A concentration-time data were in accordance with the two-compartment model. The CL and k10 of CyA-HSA significantly decreased and AUC significantly increased compared to those of Sandimmune® (P< 0. 05). CyA-HSA nanoparticles showed obvious solubility enhancement, sustained release and less side effect and toxicity resulting from solubilizing agent of Sandimmune® , Cremophor EL, and might be developed as the next generation dosage form of cyclosporine A.
Cyclosporine A-loaded human serum albumin nanoparicles(CyA-HSA)were prepared and physicochemical properties including entrapment efficiency, drug-loading capability, particles size, Zeta potential, morphology, pH value and osmotic pressure were evaluated. Dialysis was undertaken to investigate the release of CyA from CyA-HSA nanoparticles in vitro. The obtained CyA-HSA nanoparticles showed spherical shape with mean particle sizes of 240. 5 nm and Zeta potential of -32. 0 mV. The drug-loading amount and entrapment efficiency were 14. 7% and 85. 8%, respectively. The pH and osmotic pressure of nanoparticles were 7. 0 and 314. 7 mOsmol/kg, respectively. CyA-HSA nanoparticles exhibited better dilution stability than commercial cyclosporine A injection, Sandimmune® . Both CyA-HSA and Sandimmune® exhibited significant sustained release behavior in vitro and both release profiles displayed a zero-order process. The pharmacokinetic study at equal administration dosage(7 mg/kg)in rats showed that cyclosporine A concentration-time data were in accordance with the two-compartment model. The CL and k10 of CyA-HSA significantly decreased and AUC significantly increased compared to those of Sandimmune® (P< 0. 05). CyA-HSA nanoparticles showed obvious solubility enhancement, sustained release and less side effect and toxicity resulting from solubilizing agent of Sandimmune® , Cremophor EL, and might be developed as the next generation dosage form of cyclosporine A.
2013, 44(3): 244-248.
DOI: 10.11665/j.issn.1000-5048.20130311
Abstract：
Liposomes with different surface characteristics were prepared based on different lipid materials and preparation conditions. Paclitaxel(PTX)was selected as the model drug. The release characteristics of these liposomes were investigated. The uptaken of liposomes of different surface properties in hepatocellular carcinoma cells were studied through cellular uptaken experiment. All these liposomes showed sustained release property, as their accumulative release amounts were less than 30% in 48 h. The cytotoxicity of every preparation was evaluated with MTT method. Hepatocellular carcinoma cells survived more than 80% when the concentration of PTX was below 50 μg/mL in 48 h. The effect of different surface characteristics on uptake of liposomes by hepatocellular carcinoma cell lines(BEL-7402 cells and HepG2 cells)was investigated through quantification of PTX in cells. Cell uptake results indicated that preparations with smaller size or higher Zeta potential showed more PTX uptake.
Liposomes with different surface characteristics were prepared based on different lipid materials and preparation conditions. Paclitaxel(PTX)was selected as the model drug. The release characteristics of these liposomes were investigated. The uptaken of liposomes of different surface properties in hepatocellular carcinoma cells were studied through cellular uptaken experiment. All these liposomes showed sustained release property, as their accumulative release amounts were less than 30% in 48 h. The cytotoxicity of every preparation was evaluated with MTT method. Hepatocellular carcinoma cells survived more than 80% when the concentration of PTX was below 50 μg/mL in 48 h. The effect of different surface characteristics on uptake of liposomes by hepatocellular carcinoma cell lines(BEL-7402 cells and HepG2 cells)was investigated through quantification of PTX in cells. Cell uptake results indicated that preparations with smaller size or higher Zeta potential showed more PTX uptake.
2013, 44(3): 249-252.
DOI: 10.11665/j.issn.1000-5048.20130312
Abstract：
An ultra-performance liquid chromatographic method was established for the simultaneous determination of seven active compounds in Huoxiang Zhengqi liquid. Seven compounds were analyzed simultaneously with an Acquity BEH C18 column by gradient elution using acetonitrile-0. 1% phosphoric acid as the mobile phase. The column was maintained at 35 °C; the flow rate was 0. 4 mL/min; the detection wavelengths were set at 249, 284 and 336 nm, respectively. Good linearity(r> 0. 999 9)in the range of the test concentration was observed between concentration and chromatographic response of each compound, and the average recoveries of the method were between 96. 16% and 103. 4%.
An ultra-performance liquid chromatographic method was established for the simultaneous determination of seven active compounds in Huoxiang Zhengqi liquid. Seven compounds were analyzed simultaneously with an Acquity BEH C18 column by gradient elution using acetonitrile-0. 1% phosphoric acid as the mobile phase. The column was maintained at 35 °C; the flow rate was 0. 4 mL/min; the detection wavelengths were set at 249, 284 and 336 nm, respectively. Good linearity(r> 0. 999 9)in the range of the test concentration was observed between concentration and chromatographic response of each compound, and the average recoveries of the method were between 96. 16% and 103. 4%.
2013, 44(3): 253-256.
DOI: 10.11665/j.issn.1000-5048.20130313
Abstract：
S180 tumor-bearing mice were used to study the pharmacokinetics and biodistribution in lung, bone and tumor issues of vinorelbine-loaded liposome(L-NVB)and vinorelbine injection(NVB) in vivo. AUC 0-∞ and cmax of L-NVB higher than NVB, indicating its potential to improve theraputic effectiveness. While the decrease of CLz and the increase of MRT of L-NVB revealed that the liposomes could prolong the resistance time in blood and increase the drug amount that diffused into tumor tissues. Although the elimination tendency in lung, bone and tumor was similar, L-NVB displayed significantly decreased bone accumulation(P< 0. 01)and significantly increased tumor accumulation(P< 0. 001)compared with common NVB. These results demonstrated L-NVB could accumulate in tumor tissue due to enhanced permeability and retention effect, which improved the tumor targeting capability and reduced the drug dosage in other tissue such as bone. L-NVB showed better clinical potential with reduced toxicity and improved theraputic effectiveness.
S180 tumor-bearing mice were used to study the pharmacokinetics and biodistribution in lung, bone and tumor issues of vinorelbine-loaded liposome(L-NVB)and vinorelbine injection(NVB) in vivo. AUC 0-∞ and cmax of L-NVB higher than NVB, indicating its potential to improve theraputic effectiveness. While the decrease of CLz and the increase of MRT of L-NVB revealed that the liposomes could prolong the resistance time in blood and increase the drug amount that diffused into tumor tissues. Although the elimination tendency in lung, bone and tumor was similar, L-NVB displayed significantly decreased bone accumulation(P< 0. 01)and significantly increased tumor accumulation(P< 0. 001)compared with common NVB. These results demonstrated L-NVB could accumulate in tumor tissue due to enhanced permeability and retention effect, which improved the tumor targeting capability and reduced the drug dosage in other tissue such as bone. L-NVB showed better clinical potential with reduced toxicity and improved theraputic effectiveness.
2013, 44(3): 257-262.
DOI: 10.11665/j.issn.1000-5048.20130314
Abstract：
The aim of study was to determine the relationship between the biomarker of glucose and lipid metabolism and NG, NG′-asymmetric dimethylarginine(ADMA), total homocysteine(tHcy), adiponectin(APN)and pentraxin 3(PTX3)in type 2 diabetes mellitus rats. Diabetes was induced in Sprague-Dawley rats by a single intraperitoneal injection of 35mg/kg streptozotocin(STZ). Before and 2nd, 4th, 7th, 9th weeks after STZ injection, fasting plasma glucose(FPG), fasting insulin(FINS), OGTT, serum lipid(TC, TG and LDL-C), ADMA, tHcy, APN, PTX3 were determined. Compared with the groups of control and high fat diet(HFD), FPG, Homeostasis model assessment for insulin resistence index(HOMA-IR), TC, TG and LDL-C level of type 2 diabetes mellitus(T2DM)groups were significantly increased. In T2DM group, the concentration of ADMA increased gradually, tHcy decreased by degrees, APN reduced significantly, the PTX3 elevated remarkably. Our results indicate that ADMA, tHcy, APN, PTX3 are well correlated with glucose and lipid metabolism biomarkers. The plurality of biomarkers mentioned before should be monitored to evaluate the cardiovascular risk of type 2 diabetes mellitus.
The aim of study was to determine the relationship between the biomarker of glucose and lipid metabolism and NG, NG′-asymmetric dimethylarginine(ADMA), total homocysteine(tHcy), adiponectin(APN)and pentraxin 3(PTX3)in type 2 diabetes mellitus rats. Diabetes was induced in Sprague-Dawley rats by a single intraperitoneal injection of 35mg/kg streptozotocin(STZ). Before and 2nd, 4th, 7th, 9th weeks after STZ injection, fasting plasma glucose(FPG), fasting insulin(FINS), OGTT, serum lipid(TC, TG and LDL-C), ADMA, tHcy, APN, PTX3 were determined. Compared with the groups of control and high fat diet(HFD), FPG, Homeostasis model assessment for insulin resistence index(HOMA-IR), TC, TG and LDL-C level of type 2 diabetes mellitus(T2DM)groups were significantly increased. In T2DM group, the concentration of ADMA increased gradually, tHcy decreased by degrees, APN reduced significantly, the PTX3 elevated remarkably. Our results indicate that ADMA, tHcy, APN, PTX3 are well correlated with glucose and lipid metabolism biomarkers. The plurality of biomarkers mentioned before should be monitored to evaluate the cardiovascular risk of type 2 diabetes mellitus.
2013, 44(3): 263-266.
DOI: 10.11665/j.issn.1000-5048.20130315
Abstract：
To evaluate the anti-human hepatocellular carcinoma activity of turmeric oil(TO). Cell viability was assessed by MTT assay, cell apoptosis and mitochondrial membrane potential were measured by flow cytometry. The protein abundance of Bax, Bcl-2, caspase-3, caspase-9 and cytochrome C was analyzed by Western blot. The results demonstrated TO-induced apoptosis of Bel-7402 cells in a time- and dose- dependent manners. It was characterized by loss of mitochondrial membrane potential(ΔΨm)and enhanced Bax/Bcl-2 ratio. The release of cytochrome C from mitochondria and the activation of caspase-9 and -3 indicated that TO might induce apoptosis of Bel-7402 cells via mitochondrial-mediated pathway.
To evaluate the anti-human hepatocellular carcinoma activity of turmeric oil(TO). Cell viability was assessed by MTT assay, cell apoptosis and mitochondrial membrane potential were measured by flow cytometry. The protein abundance of Bax, Bcl-2, caspase-3, caspase-9 and cytochrome C was analyzed by Western blot. The results demonstrated TO-induced apoptosis of Bel-7402 cells in a time- and dose- dependent manners. It was characterized by loss of mitochondrial membrane potential(ΔΨm)and enhanced Bax/Bcl-2 ratio. The release of cytochrome C from mitochondria and the activation of caspase-9 and -3 indicated that TO might induce apoptosis of Bel-7402 cells via mitochondrial-mediated pathway.
2013, 44(3): 267-271.
DOI: 10.11665/j.issn.1000-5048.20130316
Abstract：
A novel podophyllotoxin derivative, 4β-(1, 3, 4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin(OAMDP), showed the antiproliferative effect, for which OAMDP could suppress the proliferation of HeLa cells in a dose-and time-dependent manner. Furthermore, its molecular mechanism in HeLa cells was investigated. In HeLa cells treated by OAMDP, topical morphological changes of apoptotic body formation were observed by Hoechst 33258 staining. Cell apoptosis was also confirmed by Annexin Ⅴ-FITC/PI double staining assay. Rhodamine 123 label testing revealed that the mitochondrial membrane potential(ΔΨm)of cells was decreased. OAMDP increased apoptotic cell population by induction of bax and reduction of Bcl-2 expression. Moreover, cell cycle analysis showed that OAMDP induced S phase arrest in HeLa cells. Our results indicated that OAMDP, with the ability to cause cell cycle S arrest and apoptosis, has the potential to become a novel antitumor agent.
A novel podophyllotoxin derivative, 4β-(1, 3, 4-oxadiazole-2-amino-5-methyl)-4-deoxypodophyllotoxin(OAMDP), showed the antiproliferative effect, for which OAMDP could suppress the proliferation of HeLa cells in a dose-and time-dependent manner. Furthermore, its molecular mechanism in HeLa cells was investigated. In HeLa cells treated by OAMDP, topical morphological changes of apoptotic body formation were observed by Hoechst 33258 staining. Cell apoptosis was also confirmed by Annexin Ⅴ-FITC/PI double staining assay. Rhodamine 123 label testing revealed that the mitochondrial membrane potential(ΔΨm)of cells was decreased. OAMDP increased apoptotic cell population by induction of bax and reduction of Bcl-2 expression. Moreover, cell cycle analysis showed that OAMDP induced S phase arrest in HeLa cells. Our results indicated that OAMDP, with the ability to cause cell cycle S arrest and apoptosis, has the potential to become a novel antitumor agent.
2013, 44(3): 272-276.
DOI: 10.11665/j.issn.1000-5048.20130317
Abstract：
Recombinant protein of vancomycin glycosyltransferase, GtfE, was obtained by gene cloning and hete-rologous expression. Gene gtfE was amplified from the genomic DNA of vancomycin producing strain and ligated into expression vector pET-37b, the recombinant plasmid GtfE/pET-37b was transformed into E. coli BL21(DE3). The product of in vitro glucosylation reaction catalyzed by purified GtfE was isolated and identified by HPLC and ESI-MS, respectively. The assay indicated that the recombinant protein GtfE had expected glucosylation activity to transfer uridine 5′-diphosphoglucose to the vancomycin aglycone. This study laid the foundation for producing glycosyl diversity of vancomycin.
Recombinant protein of vancomycin glycosyltransferase, GtfE, was obtained by gene cloning and hete-rologous expression. Gene gtfE was amplified from the genomic DNA of vancomycin producing strain and ligated into expression vector pET-37b, the recombinant plasmid GtfE/pET-37b was transformed into E. coli BL21(DE3). The product of in vitro glucosylation reaction catalyzed by purified GtfE was isolated and identified by HPLC and ESI-MS, respectively. The assay indicated that the recombinant protein GtfE had expected glucosylation activity to transfer uridine 5′-diphosphoglucose to the vancomycin aglycone. This study laid the foundation for producing glycosyl diversity of vancomycin.
2013, 44(3): 277-282.
DOI: 10.11665/j.issn.1000-5048.20130318
Abstract：
The extent of drug distribution in body, including volume of distribution and tissue-to-plasma partition coefficients, is an important indicator to evaluate drug efficacy and adverse effect. Considering the ethical issue, the two parameters can not be directly measured in human, therefore, it is significant to predict the volume of distribution and the tissue-to-plasma partition coefficients accurately. This paper reviewes recent developments in prediction of volume of distribution at steady-state based on empirical method, half-mechanistic method and physiologically-based pharmacokinetic model, respectively.
The extent of drug distribution in body, including volume of distribution and tissue-to-plasma partition coefficients, is an important indicator to evaluate drug efficacy and adverse effect. Considering the ethical issue, the two parameters can not be directly measured in human, therefore, it is significant to predict the volume of distribution and the tissue-to-plasma partition coefficients accurately. This paper reviewes recent developments in prediction of volume of distribution at steady-state based on empirical method, half-mechanistic method and physiologically-based pharmacokinetic model, respectively.
2013, 44(3): 283-288.
DOI: 10.11665/j.issn.1000-5048.20130319
Abstract：
Recombinant human follicle-stimulating hormone, rhFSH, is now commonly used in human assistant reproductive technology. However, rhFSH is difficult to be produced by prokaryotic expression system due to its glycosylation, so there are now only two brands of rhFSH in clinics. In the future, it is necessary to develop high expression cell lines to increase rhFSH yield in the process. And the homogeneity of glycosylation of rhFSH will be primarily considered in the production. This review summarizes the advances of the development of rhFSH and its mutants, and lays the foundation for the further research of rhFSH.
Recombinant human follicle-stimulating hormone, rhFSH, is now commonly used in human assistant reproductive technology. However, rhFSH is difficult to be produced by prokaryotic expression system due to its glycosylation, so there are now only two brands of rhFSH in clinics. In the future, it is necessary to develop high expression cell lines to increase rhFSH yield in the process. And the homogeneity of glycosylation of rhFSH will be primarily considered in the production. This review summarizes the advances of the development of rhFSH and its mutants, and lays the foundation for the further research of rhFSH.
