AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differentia...AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells were exposedto GA for 24, 48 and 72 h, the IC50 value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 μmol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by AnnexinV/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 μmol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo.展开更多
Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and...Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.展开更多
Peptide nucleic acids (PNA) oligomers were synthesized in most cases by peptide synthesis from N-protected monomers. In this work a new method of obtaining PNA monomer by Ugi four-component condensation reaction was t...Peptide nucleic acids (PNA) oligomers were synthesized in most cases by peptide synthesis from N-protected monomers. In this work a new method of obtaining PNA monomer by Ugi four-component condensation reaction was tested by solid-phase synthesis. The Fmoc protected PNA monomer was build up with thymin-1-yl acetic acid, 3-methylbutyl aldehyde, Fmoc protected aminoethyl isocyanide and Gly-Wang resin.展开更多
Based on the structure-activity relationships of RGD-containing peptides, a series of 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. All of them were first reported. Their structures were confirmed b...Based on the structure-activity relationships of RGD-containing peptides, a series of 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. All of them were first reported. Their structures were confirmed by spectral data and elemental analysis. Their ability to inhibit angiogenesis were evaluated in the chick embryo chorioallantoic membrane assay at 10-5 mol/L. Compounds 5b and 5e displayed obviously antiangiogenic activity.展开更多
Methetraxate(MTX),a classical dihydrofolate reductase inhibitor,was a successful clinical antitumor agent,having potent inhibitory activities to several kinds of tumors.Unfortunately,the cancer cellks were easier to p...Methetraxate(MTX),a classical dihydrofolate reductase inhibitor,was a successful clinical antitumor agent,having potent inhibitory activities to several kinds of tumors.Unfortunately,the cancer cellks were easier to produce resistance to MTX which ended in the failure of chemotherapy.In order to overcome the resistance of tumor cells,a new kind of dihydrofolate reductase inhibitors called nonclassical antifolate including triazines,pyrimidines and quinazolines were designed and synthesized.Because of the different antitumor mechanisms between the two kinds of compunds,the cancer cells resistant to MTX may still be sensitive to the nonclassical antifolate.According to this theory,some nonclassical antifolate 2,4-diamino-5-methyl-6-(substituted benzylamino)quinazolines with the general structure shown in FIg.1 were synthesized and their antitumor activities were determined in this thesis.展开更多
Some oligopeptides and peptoids were synthesized by applying the organophosphorus compound DEPBT as a coupling reagent. D-Biotin-OOBt was obtained unexpectedly. A proposed reaction mechanism for DEPBT-mediated coupl...Some oligopeptides and peptoids were synthesized by applying the organophosphorus compound DEPBT as a coupling reagent. D-Biotin-OOBt was obtained unexpectedly. A proposed reaction mechanism for DEPBT-mediated coupling was proved.展开更多
Recently, it has been reported that the luteolytic ac-tion was the main mechanism of the termination of earlypregnancy by contraceptivest. In addition, some estro-gen receptor ligands such as droloxifene have beenshow...Recently, it has been reported that the luteolytic ac-tion was the main mechanism of the termination of earlypregnancy by contraceptivest. In addition, some estro-gen receptor ligands such as droloxifene have beenshown to inhibit the growth of cultured rat luteal cells.It has been known that 2-phenylindole derivatives couldcompete with estradiol for the estrogen receptor. Theseresults prompted us to design and synthesize the follow-ing six new 3-oxamoyl-2-phenylindole compounds 1a-fand test their effects on the growth of luteal cells, aimingat seeking new lead compounds possessing antifertility activities.展开更多
Ugi-4CC(four-component condensation) reaction is one of isonitrile-based MCR's(multicomponent reactions), which is started with an amine, an aldehyde, a carboxylic acid and an isocyanide, after full use of the spe...Ugi-4CC(four-component condensation) reaction is one of isonitrile-based MCR's(multicomponent reactions), which is started with an amine, an aldehyde, a carboxylic acid and an isocyanide, after full use of the specialty of isonitrile and be used to build a series of compounds with different structural skeletons by using diverse inputs. In our work, two kinds of isonitriles were synthesized and a parallel synthesis of an α-acylarnino amide library was performed to modify the Ugi reaction conditions.展开更多
Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cance...Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cancer, the results of the preliminary pharmacological screening showed that compound 6c, i.e. 17-(2'-oxazoly)-androsta-5,16-diene-3-ol was a strong inhibitor, comparable with that of the reference compound VN-85. The introduction ofmethyl or phenyl group at the 4' or 5' position of oxazole ring decreased the activity. The in vitro activities of 3- acetate 5a-c and 8 were lower than their 3-ol counterparts 6a-c and 9 as expected. The further pharmacological study of 6c is in progress.展开更多
S-akyl thiobenzoate compounds were designed as farnesyltransferase (FTase) inhibitors.An effective synthetic method was explored. The structures of the target compounds wereelucidated by NMR spectral and elemental ana...S-akyl thiobenzoate compounds were designed as farnesyltransferase (FTase) inhibitors.An effective synthetic method was explored. The structures of the target compounds wereelucidated by NMR spectral and elemental analysis.展开更多
Endogenous inhibitors of nitric oxide synthase are considered to be a contributor to endothelium dysfunction,and the increased level of them is related to the elevation of lipid peroxides.The present study examined th...Endogenous inhibitors of nitric oxide synthase are considered to be a contributor to endothelium dysfunction,and the increased level of them is related to the elevation of lipid peroxides.The present study examined the antioxidation of demethylbellidifolin(DMB),a xanthone compound,and the protective effect of the drug on endothelial cells in rats.DMB significantly inhibited Cu^2+-induced LDL oxidation and scavenged DPPH radicals.DMB(10 or 30μmol·L^-1) significantly attenuated the inhibition by lysophosphatidylcholine of endothelium-dependent relaxation.DMB(60 or 120mg·kg^-1) significantly improved the endothelium-dependent relaxation and decreased the concentrations of asymmetric dimethylarginine(ADMA) and malondialdehyde induced by a single injection of low density lipoprotein(LDL).The present results suggest that DMB preserves endothelial cells in the rats treated with LDL and the protective effect of DMB on endothelium is related to the reduction of ADMA concentration by inhibiting lipid peroxidation.展开更多
A series of 1-[2-(substituted phenoxy)ethyl]-4-(2-methoxyphenyl)-piperazine deriva- tives have been synthesized. The radioligand receptor binding assay indicated that most of them bind with α1-adrenoceptor specific...A series of 1-[2-(substituted phenoxy)ethyl]-4-(2-methoxyphenyl)-piperazine deriva- tives have been synthesized. The radioligand receptor binding assay indicated that most of them bind with α1-adrenoceptor specifically, and one of the compound possessed subtype A selectivity.展开更多
A series of 3-methoxycarbonylpropoxy-7-(imidazol-4-ylpropinamide)-1, 3-dihydrogen- 1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-ones, as farnesyltransferase(Ftase) inhibitors, were synthesized. The preparation of the ke...A series of 3-methoxycarbonylpropoxy-7-(imidazol-4-ylpropinamide)-1, 3-dihydrogen- 1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-ones, as farnesyltransferase(Ftase) inhibitors, were synthesized. The preparation of the key intermediate, 7-amino-3-methoxycabonylpropoxy-1- methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, was improved.展开更多
Dideoxy-2'-fluoro-3'-hydroxymethylarabinofuranosylthymine 10 and cytosine 12 were synthesized from L-xylose and were found to be inactive against HIV-1 in acutely infected lymphocytes.
Herein we reported a one-pot synthesis of arylsubstituted imidazolin-2-ones by the cyclization of α-aminoacetophenone hydrochloride analogues 2 with arylisocyanates 3. Compared with other known synthetic route, this ...Herein we reported a one-pot synthesis of arylsubstituted imidazolin-2-ones by the cyclization of α-aminoacetophenone hydrochloride analogues 2 with arylisocyanates 3. Compared with other known synthetic route, this method resulted in higher yield.展开更多
基金Supported by The National High Technology Research and Development Program Foundation of China, 863 Program, No. 2002AA2Z3112the Ministry of Education Science and Technology Program, No. 104099affiliated to National Natural Science Foundation of China, No. 30472044
文摘AIM: To investigate the anticancer effect of a traditional Chinese medicine gambogic acid (GA) in human gastric cancer line BGC-823 and further study the mechanism of apoptosis induction of GA.METHODS: Low differential human gastric cancer line BGC-823 were treated with GA at different doses and different times, the inhibitory rates were detected by MTT assay. Apoptosis induced by GA in BGC-823 cells was observed by Annexin-V/PI doubling staining flow cytometry assay. And T/C (%) was chosen to detect the inhibition of GA on human gastric adenocarcinoma BGC-823 nude mice xenografts. Apoptosis on nude mice xenografts was observed by Annexin-V/PI doubling staining flow cytometry assay and DNA fragmentation assay. To further determine the molecular mechanism of apoptosis induced by GA, the changes on the expression of bcl-2 and bax genes were detected by RT-PCR.RESULTS: After incubation with GA, low differential human gastric cancer line BGC-823 was dramatically inhibited in a dose-dependent manner. After these cells were exposedto GA for 24, 48 and 72 h, the IC50 value was 1.02±0.05, 1.41±0.20 and 1.14±0.19 μmol/L, respectively. Apoptosis in BGC-823 cells induced by GA was observed by AnnexinV/PI doubling staining flow cytometry assay. The apoptotic population of BGC-823 cells was about 12.96% and 24.58%, respectively, when cells were incubated with 1.2 μmol/L GA for 48 and 72 h. T/C (%) of human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts was 44.3, when the nude mice were treated with GA (8 mg/kg). Meanwhile, apoptosis induced by GA was observed in human gastric carcinoma adenocarcinoma BGC-823 nude mice xenografts. The increase of bax gene and the decrease of bc1-2 gene expressions were found by RT-PCR.CONCLUSION: The inhibition of GA on human gastric cancer line BGC-823 was confirmed. This effect connects with the inducing apoptosis in BGC-823 cells and the molecular mechanism might be related to the reduction of expression of apoptosis-regulated gene bcl-2, and the improvement of the expression of apoptosis-regulated gene bax. The result was also confirmed in vivo.
文摘Aim The biophore of uroselective α_1-adrenoceptor antagonist was studied byusing Apex-3D software on an 02 Silicon Graphics Computer Station. Methods Five known antagonists(Indoramin, GG-818, RS100975, R-YM12167, and KMD-3213), which possess both good selectivity and highaffinities to prostate and α_1-AR subtype, were chosen for building the biophore. Using anautomatic filtering software for obtaining reasonable biophores, the filter parameters wereselected: P (probability) > 0.8, active (number of active compounds) ≥ 4, and size (descriptorcenter) ≥ 3. Results Three biophores conformed to the requirements, each of whom contained a basiccenter, an aromatic ring center and H-site according to the structure-activity relationships ofknown α_1-adrenoceptor antagonist. Conclusion The biophore model developed by computer simulationwith Apex-3D software can be used to design and synthesize a new α_1-adrenoceptor antagonist withhigh activity and low side effect.
基金This work was supposed by the National Basic Research Program(973 Program)from the Ministry of Science and Technology of China(G1998051114)the National Natural Science Foundation of China(20272004)
文摘Peptide nucleic acids (PNA) oligomers were synthesized in most cases by peptide synthesis from N-protected monomers. In this work a new method of obtaining PNA monomer by Ugi four-component condensation reaction was tested by solid-phase synthesis. The Fmoc protected PNA monomer was build up with thymin-1-yl acetic acid, 3-methylbutyl aldehyde, Fmoc protected aminoethyl isocyanide and Gly-Wang resin.
文摘Based on the structure-activity relationships of RGD-containing peptides, a series of 1,3-dihydro-1,3-dioxo-2H-isoindole derivatives were synthesized. All of them were first reported. Their structures were confirmed by spectral data and elemental analysis. Their ability to inhibit angiogenesis were evaluated in the chick embryo chorioallantoic membrane assay at 10-5 mol/L. Compounds 5b and 5e displayed obviously antiangiogenic activity.
文摘Methetraxate(MTX),a classical dihydrofolate reductase inhibitor,was a successful clinical antitumor agent,having potent inhibitory activities to several kinds of tumors.Unfortunately,the cancer cellks were easier to produce resistance to MTX which ended in the failure of chemotherapy.In order to overcome the resistance of tumor cells,a new kind of dihydrofolate reductase inhibitors called nonclassical antifolate including triazines,pyrimidines and quinazolines were designed and synthesized.Because of the different antitumor mechanisms between the two kinds of compunds,the cancer cells resistant to MTX may still be sensitive to the nonclassical antifolate.According to this theory,some nonclassical antifolate 2,4-diamino-5-methyl-6-(substituted benzylamino)quinazolines with the general structure shown in FIg.1 were synthesized and their antitumor activities were determined in this thesis.
文摘Some oligopeptides and peptoids were synthesized by applying the organophosphorus compound DEPBT as a coupling reagent. D-Biotin-OOBt was obtained unexpectedly. A proposed reaction mechanism for DEPBT-mediated coupling was proved.
文摘Recently, it has been reported that the luteolytic ac-tion was the main mechanism of the termination of earlypregnancy by contraceptivest. In addition, some estro-gen receptor ligands such as droloxifene have beenshown to inhibit the growth of cultured rat luteal cells.It has been known that 2-phenylindole derivatives couldcompete with estradiol for the estrogen receptor. Theseresults prompted us to design and synthesize the follow-ing six new 3-oxamoyl-2-phenylindole compounds 1a-fand test their effects on the growth of luteal cells, aimingat seeking new lead compounds possessing antifertility activities.
文摘Ugi-4CC(four-component condensation) reaction is one of isonitrile-based MCR's(multicomponent reactions), which is started with an amine, an aldehyde, a carboxylic acid and an isocyanide, after full use of the specialty of isonitrile and be used to build a series of compounds with different structural skeletons by using diverse inputs. In our work, two kinds of isonitriles were synthesized and a parallel synthesis of an α-acylarnino amide library was performed to modify the Ugi reaction conditions.
文摘Several 4'- and 5'-substituted 17-(2'-oxazolyl)-androsta-5,16-diene derivatives were designed and synthesized as inhibitors of 17α-hydroxylase/C17,20 -Lyase (P45017α) for the treatment of prostatic cancer, the results of the preliminary pharmacological screening showed that compound 6c, i.e. 17-(2'-oxazoly)-androsta-5,16-diene-3-ol was a strong inhibitor, comparable with that of the reference compound VN-85. The introduction ofmethyl or phenyl group at the 4' or 5' position of oxazole ring decreased the activity. The in vitro activities of 3- acetate 5a-c and 8 were lower than their 3-ol counterparts 6a-c and 9 as expected. The further pharmacological study of 6c is in progress.
基金This work was supported by National Basic Research Program(973 Program:G1998051102).
文摘S-akyl thiobenzoate compounds were designed as farnesyltransferase (FTase) inhibitors.An effective synthetic method was explored. The structures of the target compounds wereelucidated by NMR spectral and elemental analysis.
文摘Endogenous inhibitors of nitric oxide synthase are considered to be a contributor to endothelium dysfunction,and the increased level of them is related to the elevation of lipid peroxides.The present study examined the antioxidation of demethylbellidifolin(DMB),a xanthone compound,and the protective effect of the drug on endothelial cells in rats.DMB significantly inhibited Cu^2+-induced LDL oxidation and scavenged DPPH radicals.DMB(10 or 30μmol·L^-1) significantly attenuated the inhibition by lysophosphatidylcholine of endothelium-dependent relaxation.DMB(60 or 120mg·kg^-1) significantly improved the endothelium-dependent relaxation and decreased the concentrations of asymmetric dimethylarginine(ADMA) and malondialdehyde induced by a single injection of low density lipoprotein(LDL).The present results suggest that DMB preserves endothelial cells in the rats treated with LDL and the protective effect of DMB on endothelium is related to the reduction of ADMA concentration by inhibiting lipid peroxidation.
文摘A series of 1-[2-(substituted phenoxy)ethyl]-4-(2-methoxyphenyl)-piperazine deriva- tives have been synthesized. The radioligand receptor binding assay indicated that most of them bind with α1-adrenoceptor specifically, and one of the compound possessed subtype A selectivity.
文摘A series of 3-methoxycarbonylpropoxy-7-(imidazol-4-ylpropinamide)-1, 3-dihydrogen- 1-methyl-5-phenyl-2H-1, 4-benzodiazepin-2-ones, as farnesyltransferase(Ftase) inhibitors, were synthesized. The preparation of the key intermediate, 7-amino-3-methoxycabonylpropoxy-1- methyl-5-phenyl-2H-1,4-benzodiazepin-2-one, was improved.
文摘Dideoxy-2'-fluoro-3'-hydroxymethylarabinofuranosylthymine 10 and cytosine 12 were synthesized from L-xylose and were found to be inactive against HIV-1 in acutely infected lymphocytes.
文摘Herein we reported a one-pot synthesis of arylsubstituted imidazolin-2-ones by the cyclization of α-aminoacetophenone hydrochloride analogues 2 with arylisocyanates 3. Compared with other known synthetic route, this method resulted in higher yield.
