A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity an...A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.展开更多
Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactio...Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.展开更多
Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison w...Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison with authentic samples on the basis of HPLC analysis. The conversion percentage of nucleoside indicated that N- (O, O-diisopropyl) phosphoryl aspartic acid reacted with adenosine and guanosine at a much higher rate than other kinds of N- phosphoryl amino acids. while phosphorylation of cytidine and uridine was relatively easy by using N- (O, O-diisopropyl) phosphoryl threonine. The result could give some clue to the prebiotic code origin of nucleic acid and protein.展开更多
Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to repo...Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin （CPT） and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin （1） and 10-hydroxycamptothecin （2） derivatives （1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e） were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua H＆#252;bner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.展开更多
The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP...The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP-β-A1a） and N-phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, and four nucleosides, adenosine （A）, guanosine （G）, cytidine （C） and uridine （U）, were studied by electrospray ionization tandem mass spectrometry （ESI-MS/MS） and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.展开更多
Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely cl...Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.展开更多
In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR ...In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR and MS methods. The results indicated that the reactivity of phosphoryl biological small molecules was depended on the configuration, function groups and positions.展开更多
Objectives.To observe if lysophosphatidic acid(LPA)can influence nuclear nucleoside triphos-phatase(NTPase)activity of isolated hepatocyte from rat,and to investigate the possible mechanisms by which LPA affects the N...Objectives.To observe if lysophosphatidic acid(LPA)can influence nuclear nucleoside triphos-phatase(NTPase)activity of isolated hepatocyte from rat,and to investigate the possible mechanisms by which LPA affects the NTPase.Method.Isolated and cultured hepatocytes from rat liver were exposed to LPA(1×10 -9 ,1×10 -8 and5×10 -8 mol/L)with or without inhibitors of protein kinase C(PKC)and mitogen activating protein kinase kinase(MAPKK),and the NTPase activity on nuclear envelope was assayed using ATP and GTP as substrate,respectively.Results.Nuclear NTPase activity of rat hepatocytes was potently stimulated by incubation of hepato-cytes with LPA in concentration?and time ?dependent manners.In hepatocytes incubated with LPA,nu-clear NTPase activity was significantly higher than that of the control(P<0.01).In hepatocytes preincu-bated with PKC inhibitor H-7or MAPKK inhibitor PD98059,LPA-stimulated activation of nuclear NT-Pase was obviously attenuated.In addition,direct incubation of isolated hepatic nuclei with LPA had no effect on nuclear NTPase activity.Conclusion.LPA is involved in modulating nuclear NTPase activity in hepatocytes.The stimulating effect of LPA on the nuclear NTPase is mediated at least partly by PKC and MAPK-dependent pathway.展开更多
A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives...A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives and amines can produce yields ranging from 50% to 85% of the resulting amide.展开更多
Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified ...Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.展开更多
文摘A series of novel L-amino acid esters prodrugs of acyclic nucleoside phosphonates was synthesized and their anti-HBV activity was evaluated in HepG2 2.2.15 cells. Compound 1d exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with EC50 and CC50 values of 0.207 μmol/L and 2530 μmol/L, respectively.
文摘Facile direct esterification reactions between 2′,3′-O-isopropylidene-nucleosides and Fmoc- or trityl-protected amino acids %via% N,N-dicyclohexyl-carbodiimide(DCC) mediated condensation are described. These reactions offer a mild and convenient method to synthesize aminoacylated nucleoside derivatives.
基金This prqiect was supported by the National Natural Science Foundation of China, National Science Technology Committee of Chi
文摘Nucleosides were phosphorylated with different N- (O, O-diisopropyl) phosphoryl amino acids to give nucleoside mono phosphates in aqueous solution. 2', 3', and 5'-isomers had been confirmed by comparison with authentic samples on the basis of HPLC analysis. The conversion percentage of nucleoside indicated that N- (O, O-diisopropyl) phosphoryl aspartic acid reacted with adenosine and guanosine at a much higher rate than other kinds of N- phosphoryl amino acids. while phosphorylation of cytidine and uridine was relatively easy by using N- (O, O-diisopropyl) phosphoryl threonine. The result could give some clue to the prebiotic code origin of nucleic acid and protein.
基金supported by the National Natural Science Foundation of China (31171878,31071707 and 31000851)
文摘Creating high-efifcient and environment-friendly pesticides is very important to produce the pollution free agriculture food and maintain the balance of the survival environmental of the human being. According to reports, camptothecin （CPT） and its derivatives are now being explored as a class of botanical insecticide in agriculture due to its novel mode of action. In order to improve the insecticidal activity of CPT, ten novel camptothecin （1） and 10-hydroxycamptothecin （2） derivatives （1a, 1b, 1c, 1d, 1e;2a, 2b, 2c, 2d, 2e） were designed and synthesized via esteriifcation with analogs of chrysanthemic acid, which have outstanding insecticidal activity. The results showed that compound 2a exhibited potent antifeeding effect and the best contact toxicity among the target compounds against the third-instar larvae of beet armyworm, Spodoptera exigua H＆#252;bner. Compound 2a was also found to be the most effective cytotoxic compound to the tested insect cell lines, IOZCAS-Spex-II, which were established from the fat bodies of S. exigua. It was proposed that the 10-hydroxyl group in the camptothecin derivatives is a key factor for the antifeeding activity of a compound. The nature of the substituents was considered the major factor in determining the insecticidal activity of these compounds.
基金the National Natural Science Foundation of China(Nos.20572061,20672104)the Chinese Ministry of Education and Zhengzhou University for financial support.
文摘The reactions of four different N-（O,O＇-diisopropyl） phosphoamino acids （DIPP-aa）, such as N-phosphoryl-L-α-alanine （DIPP- L-α-Ala）, N-phosphoryl-D-α-alanine （DIPP-D-α-A1a）, N-phosphoryl-β-alanine （DIPP-β-A1a） and N-phosphoryl-γ-amino butyric acid （DIPP-γ-Aba）, and four nucleosides, adenosine （A）, guanosine （G）, cytidine （C） and uridine （U）, were studied by electrospray ionization tandem mass spectrometry （ESI-MS/MS） and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.
基金We thank for the funding support from the Hundred Talents Program of Hunan Province(No.9999004007)the Startup grant of Hunan University of Chinese Medicine(No.999900201107).
文摘Objective There are many clinical reports on traditional Chinese medicine(TCM)combined with nucleoside(acid)analogues(NAs)for the treatment of chronic hepatitis B(CHB),but its efficacy and safety are not completely clear.This meta-analysis aims to evaluate the clinical efficacy and safety thus providing evidence for clinical applications.Methods We searched Chinese databases the China National Knowledge Infrastructure(CNKI),Wanfang Data,and China Science and Technology Journal Database(VIP),as well as English databases Pub Med and Cochrane Library,from time of establishment to April 14,2021.Literature quality was evaluated according to the bias risk assessment criteria of Cochrane Collaboration network.Rev Man 5.3 and Stata 12.0 software were used to perform this research.Results A total of 23 articles,3282 patients,and 25 TCM prescriptions were included in this study.NAs plus TCM remarkably improved the clinical total effective rate[Odds ratio(OR)=3.92,P<0.00001],TCM syndrome score(Mean difference=-3.73,P<0.00001),hepatitis B virus(HBV)DNA negative conversion rate(OR=1.49,P=0.0001),hepatitis Be antigen(HBe Ag)negative conversion rate(OR=2.03,P<0.00001),alanine aminotransferase levels[Std mean difference(SMD)=-0.95,P<0.00001],and aspartate aminotransferase levels(SMD=-0.70,P=0.0004).Adverse reaction rates did not increase in the combined treatment group(OR=0.97,P=0.84).A comprehensive analysis of the 25 TCM prescriptions suggested that the combination of spleen-strengthening prescriptions with NAs showed better effects than other prescriptions.Conclusion TCM in combination with NAs,demonstrated better clinical efficacy against CHB than NAs alone.In addition,the combination of spleen-strengthening prescriptions and NAs was identified as the best therapeutic strategy.However,more randomized controlled trials of high quality are needed to provide more reliable clinical basis for the application of TCM.
文摘In order to further confirm the biomimic properties of N-phosphoamino acids. A series of model compounds, analogue of phosphoryl amino acids, were synthesized and their biomimic mechanism was also investigated by NMR and MS methods. The results indicated that the reactivity of phosphoryl biological small molecules was depended on the configuration, function groups and positions.
文摘Objectives.To observe if lysophosphatidic acid(LPA)can influence nuclear nucleoside triphos-phatase(NTPase)activity of isolated hepatocyte from rat,and to investigate the possible mechanisms by which LPA affects the NTPase.Method.Isolated and cultured hepatocytes from rat liver were exposed to LPA(1×10 -9 ,1×10 -8 and5×10 -8 mol/L)with or without inhibitors of protein kinase C(PKC)and mitogen activating protein kinase kinase(MAPKK),and the NTPase activity on nuclear envelope was assayed using ATP and GTP as substrate,respectively.Results.Nuclear NTPase activity of rat hepatocytes was potently stimulated by incubation of hepato-cytes with LPA in concentration?and time ?dependent manners.In hepatocytes incubated with LPA,nu-clear NTPase activity was significantly higher than that of the control(P<0.01).In hepatocytes preincu-bated with PKC inhibitor H-7or MAPKK inhibitor PD98059,LPA-stimulated activation of nuclear NT-Pase was obviously attenuated.In addition,direct incubation of isolated hepatic nuclei with LPA had no effect on nuclear NTPase activity.Conclusion.LPA is involved in modulating nuclear NTPase activity in hepatocytes.The stimulating effect of LPA on the nuclear NTPase is mediated at least partly by PKC and MAPK-dependent pathway.
基金PAPIIT/UNAM Projects No.IN200614 and IT202015 and project PIAPI VC02 for partially supporting this worka part of the Project Catedra:Diseno de Sustancias Bioactivas of FESC-UNAM-2012.
文摘A convenient and easy method is described for the formation of carboxamides from carboxylic acids and primary amines in solventless conditions using infrared (IR) light. Thus, under IR light, cinnamic acid derivatives and amines can produce yields ranging from 50% to 85% of the resulting amide.
基金the National Natural Science Foundation of China(31972048,32272339)the National Key R&D Program of China(2021YFD2100104)for financial support。
文摘Hyperuricemia is a metabolic disorder caused by abnormal purine metabolism,resulting in abnormally high serum uric acid.In this study,a novel Levilactobacillus brevis PDD-5 isolated from salty vegetables was verified with the function of alleviating hyperuricemia.The relevant effects of L.brevis PDD-5 in lowering uric acid were analyzed by in vitro and in vivo experiments.The results showed that the L.brevis PDD-5 has(68.86±15.46)%of inosine uptake capacity and(95.75±3.30)%of guanosine uptake capacity in vitro.Oral administration of L.brevis PDD-5 to hyperuricemia rats reduced uric acid,creatinine,and urea nitrogen in serum,as well as decreased inosine and guanosine levels in the intestinal contents of rats.Analysis of relevant markers in the kidney by ELISA kits revealed that L.brevis PDD-5 alleviated oxidative stress and inflammation.Moreover,the gene expression of uric acid transporter 1(URAT1)and glucose transporter 9(GLUT9)was down-regulated,and the gene expression of organic anion transporter 1(OAT1)was up-regulated after treatment with L.brevis PDD-5.Western blot analysis showed that L.brevis PDD-5 alleviated hyperuricemia-induced kidney injury through the NLRP3 pathway.The se findings suggest that L.brevis PDD-5 can lower uric acid,repair kidney damage,and also has the potential to prevent uric acid nephropathy.
