A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical wer...A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.展开更多
Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characte...Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.展开更多
Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic...Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.展开更多
Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibito...Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.展开更多
A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and...A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and incubation time. Generally, for ALA and its alkylester methanesulfonates, the cell survival rate decreases and the accumulation ability of PplX increases with the concentration and incubation time. We found that the longer carbon chain methanesulfonates（C5-S, C6-S, C8-S） exhibit better PDT effect than ALA methanesulfonate. This possibly provides a promising route to the clinical application ofPplX-mediated PDT to cancer cell.展开更多
A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray c...In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.展开更多
A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized fr...A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.展开更多
Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische...Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.展开更多
Some nucleoside carhoxylic acid derivatives,such as(±)ethyl ester of griseolic acid (4)and 9-(2'-deoxy-2'-(benzyloxycarbonyl)-methylene-β-D-rihohept-2'-enofuranosyluranate)adenine (11),were synthesiz...Some nucleoside carhoxylic acid derivatives,such as(±)ethyl ester of griseolic acid (4)and 9-(2'-deoxy-2'-(benzyloxycarbonyl)-methylene-β-D-rihohept-2'-enofuranosyluranate)adenine (11),were synthesized.The formation of lactone of 5'-deoxy-adenosineacetic acid(AAA,3)was investigated by using different reagents for lactonization from AAA,but all of the efforts failed, and sone unexpected compounds were obtained.展开更多
Reaction of heterocycle substituted telluronium salts with aroma- tic aldehydes under mild conditions gave corresponding chalcones.In the presence of dibutyl telluride,2-bromomethyl-5-nitrofuran condensed easily with ...Reaction of heterocycle substituted telluronium salts with aroma- tic aldehydes under mild conditions gave corresponding chalcones.In the presence of dibutyl telluride,2-bromomethyl-5-nitrofuran condensed easily with aromatic aldehydes in THF to afford corresponding olefin derivatives as one-pot reaction.展开更多
Eight comptexes (RC_5H_4)_2Ti(O_2CA_r)_2(R=H,CH_3;Ar= with 2 equiv.N_aO_2CA_r.The carboxytate ligands in the complexes coordinate to titan^um atom in monodentate mode.(CH_3C_5H_4)_2Ti(O_2CC_4H_3S-2)_2 has four-coordin...Eight comptexes (RC_5H_4)_2Ti(O_2CA_r)_2(R=H,CH_3;Ar= with 2 equiv.N_aO_2CA_r.The carboxytate ligands in the complexes coordinate to titan^um atom in monodentate mode.(CH_3C_5H_4)_2Ti(O_2CC_4H_3S-2)_2 has four-coordinate bent titanocene in which the thiophencarboxyaltes are a monodeotate ligand(Ti-0=1.981(8)A,1.926(3)A;) 0-Ti-0:91.6(8)~ ; Ti-C:2.333-2.440A).展开更多
2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementar...2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.展开更多
文摘A new series of N^1-acetylamino-（5-alkyl/aryl- 1,3,4-thiadiazole-2-yl）-5-fluorouracil derivatives were designed and synthesized. These compounds have not been reported in literature, and their structure chemical were confirmed by IR, ^1H NMR and MS （HRMS）. The results of antitumor inhibitory activity test showed that some compounds possess more potent antitumor inhibitory activity than 5-fluorouracil.
文摘Based on the structure-activity relationships and antiangiogenic mechanism of RGD-containing peptides, a series of 5-amino- 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. The structures were characterized by ^1H NMR, MS and elementary analysis. There ability to inhibit angiogenesis were evaluated by chick embryo chorioallantoic membrane assay at 10^-5 mol/L. Compounds 7a and 7b displayed obvious antiangiogenic activity.
基金supported by the National Natural Science Foundation of China (No. 30500339)Natural Science Foundation of Zhejiang Province (NO.Y407308)the Sprout Talented Project Program of Zhejiang Province (No. 2008R40G2020019)
文摘Quantitative structure activity relationship （QSAR） studies were performed on 45 anthranilic acid derivatives for their potent allosteric inhibition activities of HCV NSSB polymerase. Genetic algorithm based genetic function approximation （GFA） method of variable selection was used to generate the model. Highly statistically significant model with r^2 = 0.966 and r^2cv = 0.951 was obtained when the number of descriptors in the equation was set to 5. High r^2pred value of 0.884 indicates the good predictive power of the best model. Spatial descriptors of radius of gyration （RadOfGration）, molecular volume （Vm）, length of molecule in the z dimension （Shadow-Zlength）, thermodynamic descriptors of the octanol/water partition coefficient （LogP） and molecular refractivity index （MR） showed enormous contributions to HCV NS5B polymerase inhibition. The validation of the model was done by leave-one-out （LOO） test, randomization tests and external test set prediction. The model gives insight on indispensable structural requirements for the activity and can be used to design more potent analogs against HCV NSSB polymerase.
文摘Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.
基金Supported Partly by the Academic Frontier Promotion Grant from the Ministry of Education,Science,Sports and Culture,Japan and the Exchange Program Between the Japan Society of the Promotion of Science and the Chinese Academy of Sciences
文摘A series of 5-aminolevulinic acid and its alkylester methanesulfonates was exploited to photodynamic therapy（PDT） of human lymphocytic cells, U-937 in vitro. The PDT efficiency is influenced by the concentration and incubation time. Generally, for ALA and its alkylester methanesulfonates, the cell survival rate decreases and the accumulation ability of PplX increases with the concentration and incubation time. We found that the longer carbon chain methanesulfonates（C5-S, C6-S, C8-S） exhibit better PDT effect than ALA methanesulfonate. This possibly provides a promising route to the clinical application ofPplX-mediated PDT to cancer cell.
文摘A series of ethyl 6-bromo-5-hydroxyindole-3-carboxylate derivatives were synthesized and their in vitro anti-influenza virus activity was evaluated. All the compounds were characterized by 1H NMR and MS.
基金Supported by the “Climbing Program”(pdjh2019b0497)Special Funds,the Foundation of the Department of Education of Guangdong Province(2018KZDXM070,2017KZDXM085,2017KQNCX204)College Students Innovation and Entrepreneurship Training Program of Wuyi University and Foundation for Young Talents(2018KQNCX272,2018KQNCX273)
文摘In order to discover the novel antitumor agents,a series of N,N,1-triphenyl-1Hbenzo[d]imidazol-5-amine derivatives were designed and synthesized,and the structures were characterized by IR,H-RMS,1H and 13C NMR.X-ray crystallography showed that 4c is in monoclinic system,space group P1 with a=9.209(2),b=9.533(3),c=14.097(3)?,β=102.069(3)°,V=1202.2(5)?3,Z=2,F(000)=528,μ=1.74 mm–1,S=1.024,the final R=0.0448 and wR=0.1109.The in vitro antitumor activities of target compounds were evaluated by MTT assay against human cancer cell lines K562,HL-60,HeLa and BGC-823.The target compounds demonstrated weak or moderate antitumor activities against these cell lines.
基金Supported by the National Science and Technology Major Projects of China(No.2009ZX09301-012)
文摘A series of 6-fluoro-3,3a,4,5-tetrahydro-2H-pyrazolo[4,3-c]quinoline-2-carboxamide derivatives was designed based on the bioisosterism and combination principle in drug design. The target compounds were synthesized from substituted aniline through Michael addition, cyclization, Mannich reaction and condensation with 4-substituted semicarbazides, and the structures were confirmed by mass spectrometry（MS） and 1H NMR. The antifungal assay was carried out in vitro by two-fold dilution. The result shows that all the compounds are of antifungal activities against the tested fungi at different levels.
基金supported by the National Natural Science Foundation of China,No.82001604Guizhou Provincial Higher Education Science and Technology Innovation Team,No.[2023]072+1 种基金Guizhou Province Distinguished Young Scientific and Technological Talent Program,No.YQK[2023]040Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2021]-368(all to LXiong),and Zunyi City Innovative Talent Team Training Plan,No.[2022]-2.
文摘Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.
基金The project was supported by the National Natural Science Foundation of China.
文摘Some nucleoside carhoxylic acid derivatives,such as(±)ethyl ester of griseolic acid (4)and 9-(2'-deoxy-2'-(benzyloxycarbonyl)-methylene-β-D-rihohept-2'-enofuranosyluranate)adenine (11),were synthesized.The formation of lactone of 5'-deoxy-adenosineacetic acid(AAA,3)was investigated by using different reagents for lactonization from AAA,but all of the efforts failed, and sone unexpected compounds were obtained.
文摘Reaction of heterocycle substituted telluronium salts with aroma- tic aldehydes under mild conditions gave corresponding chalcones.In the presence of dibutyl telluride,2-bromomethyl-5-nitrofuran condensed easily with aromatic aldehydes in THF to afford corresponding olefin derivatives as one-pot reaction.
文摘Eight comptexes (RC_5H_4)_2Ti(O_2CA_r)_2(R=H,CH_3;Ar= with 2 equiv.N_aO_2CA_r.The carboxytate ligands in the complexes coordinate to titan^um atom in monodentate mode.(CH_3C_5H_4)_2Ti(O_2CC_4H_3S-2)_2 has four-coordinate bent titanocene in which the thiophencarboxyaltes are a monodeotate ligand(Ti-0=1.981(8)A,1.926(3)A;) 0-Ti-0:91.6(8)~ ; Ti-C:2.333-2.440A).
基金This project supported by the Natural Science Foundation of Shandong.
文摘2-Butoxy-5-fluoro-3H-4-pyrimidone derivatives of D-glucuronic acid having 0-glycosidic linkage or N-glycosidic linkage were synthesized and their anticancer activity tested.Their structures were confirmed by elementary analysis,IR spectra and ~1HNMR.
