2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl ...2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl chloride catalysts the reaction is limited to give only 1,8-dioxo-octahydroxanthenes 3a-k in very good yields.展开更多
AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination treatment.METHODS:We established and characterized a 5-FU resi...AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination treatment.METHODS:We established and characterized a 5-FU resistance(5-FU-R)cell line derived from continuous exposure(25μmol/L)to 5-FU for 20 wk in 5-FU sensitive HCT-116 cells.The proliferation and expression of different representative apoptosis and anti-apoptosis markers in 5-FU sensitive and 5-FU resistance cells were measured by the MTT assay and by Western blotting,respectively,after treatment with Resveratrol(Res)and/or 1,3-Bis(2-chloroethyl)-1-nitrosourea(BCNU).Apoptosis and cell cycle arrest was measured by 4',6'-diamidino-2-phenylindole hydrochloride staining and fluorescence-activated cell sorting analysis,respectively.The extent of DNA damage was measured by the Comet assay.We measured the visible changes in the DNA damage/repair cascade by Western blotting.RESULTS:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent manner.Combined application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual treatment.In addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive cells.We established a 5-FU resistance cell line(5-FU-R)from 5-FU-sensitive HCT-116(mismatch repair deficient)cells that was not resistant to other chemotherapeutic agents(e.g.,BCNU,Res)except 5-FU.The 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT assay.There was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU treatment.This resistant cell line overexpressed anti-apoptotic[e.g.,AKT,nuclear factorκB,FLICE-like inhibitory protein),DNA repair(e.g.,DNA polymerase beta(POL-β),DNA polymerase eta(POLH),protein Flap endonuclease 1(FEN1),DNA damage-binding protein 2(DDB2)]and 5-FU-resistance proteins(thymidylate synthase)but under expressed pro-apoptotic proteins(e.g.,DAB2,CK1)in comparison to the parental cells.Increased genotoxicity and apoptosis were observed in resistant cells after combined application of BCNU and Res in comparison to untreated or parental cells.BCNU increased the sensitivity to Res of 5-FU resistant cells compared with parental cells.Fifty percent cell death were noted in parental cells when 18μmol/L of Res was associated with fixed concentration(20μmol/L)of BCNU,but a much lower concentration of Res(8μmol/L)was needed to achieve the same effect in 5-FU resistant cells.Interestingly,increased levels of adenomatous polyposis coli and decreased levels POL-β,POLH,FEN1 and DDB2 were noted after the same combined treatment in resistant cells.CONCLUSION:BCNU combined with Res exerts a synergistic effect that may prove useful for the treatment of colon cancer and to overcome drug resistance.展开更多
An energetic salt of bis（l,5-diamino-lH-tetrazolium）3,3＂-bis（nitramino）-4, 4x-azo- furazan （C6H10N2206） was synthesized with the total yield of 61.7% by using 3,4-diaminofurazan （DAF） as the starting material...An energetic salt of bis（l,5-diamino-lH-tetrazolium）3,3＂-bis（nitramino）-4, 4x-azo- furazan （C6H10N2206） was synthesized with the total yield of 61.7% by using 3,4-diaminofurazan （DAF） as the starting material. The structure of the title compound was confirmed by NMR, IR, elemental analysis and single-crystal X-ray diffraction. It crystallizes in orthorhombic, space group P21/c with a = 10.739（2）, b = 6.4765（12）, c = 14.138（3） A, fl= 108.787（3）°, V= 930.9（3） A3, Z = 1, Mr= 486.36, Dc = 1.735 g.cm3, μ= 0.15 mm-1, F（000） = 496, R = 0.042 and wR = 0.121. The thermal stability was analyzed by subsequently differential scanning calorimetry （DSC）. And the enthalpy of formation and detonation was calculated theoretically, showing the first decomposition temperature was 142.1℃, the enthalpy of formation was 1614.23 kJ.mol1 and the detonation velocity and detonation pressure were 8.781 km.s-1 and 30.7 GPa, respectively.展开更多
The title compound 1,4-bis(benztriazol-1-ylmethyl)-2,4,5,6-trimethylbenzene crys- tallizes in the monoclinic system, space group Pbca with a = 9.842(5), b = 9.455(5), c = 22.165(12) ?, V = 2062.6(18) ?3, Dc = 1.277 ...The title compound 1,4-bis(benztriazol-1-ylmethyl)-2,4,5,6-trimethylbenzene crys- tallizes in the monoclinic system, space group Pbca with a = 9.842(5), b = 9.455(5), c = 22.165(12) ?, V = 2062.6(18) ?3, Dc = 1.277 g/cm3, Z = 4, C24H24N6, Mr = 396.49, μ(MoKa) = 0.079 mm-1 and F(000) = 840. The structure was refined to R = 0.0662 and wR = 0.1891 for 1163 observed reflections (I > 2σ(I)). The title molecule has trans-conformation about the central phenyl ring. The zigzag-like molecules are connected by face-to-face π…π stacking to form an infinite 2D layer.展开更多
Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). Th...Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.展开更多
基金support from the Research Council of University of Sistan and Baluchestan, Iran
文摘2,2'-Arylmethylene bis(3-hydroxy-5,5-dimethyl-2-cyclohexene-1-one) 4l-s produced from reaction between dimedone with various aldehydes in acetonitrile using ZnO as a catalyst;whereas in the presence of ZnO-acetyl chloride catalysts the reaction is limited to give only 1,8-dioxo-octahydroxanthenes 3a-k in very good yields.
基金Supported by Indian Council of Medical Research and Department of Biotechnology,Government of India
文摘AIM:To study the mechanism of 5-fluorouracil(5-FU)resistance in colon cancer cells and to develop strategies for overcoming such resistance by combination treatment.METHODS:We established and characterized a 5-FU resistance(5-FU-R)cell line derived from continuous exposure(25μmol/L)to 5-FU for 20 wk in 5-FU sensitive HCT-116 cells.The proliferation and expression of different representative apoptosis and anti-apoptosis markers in 5-FU sensitive and 5-FU resistance cells were measured by the MTT assay and by Western blotting,respectively,after treatment with Resveratrol(Res)and/or 1,3-Bis(2-chloroethyl)-1-nitrosourea(BCNU).Apoptosis and cell cycle arrest was measured by 4',6'-diamidino-2-phenylindole hydrochloride staining and fluorescence-activated cell sorting analysis,respectively.The extent of DNA damage was measured by the Comet assay.We measured the visible changes in the DNA damage/repair cascade by Western blotting.RESULTS:The widely used chemotherapeutic agents BCNU and Res decreased the growth of 5-FU sensitive HCT-116 cells in a dose dependent manner.Combined application of BCNU and Res caused more apoptosis in5-FU sensitive cells in comparison to individual treatment.In addition,the combined application of BCNU and Res caused a significant decrease of major DNA base excision repair components in 5-FU sensitive cells.We established a 5-FU resistance cell line(5-FU-R)from 5-FU-sensitive HCT-116(mismatch repair deficient)cells that was not resistant to other chemotherapeutic agents(e.g.,BCNU,Res)except 5-FU.The 5-FU resistance of 5-FU-R cells was assessed by exposure to increasing concentrations of 5-FU followed by the MTT assay.There was no significant cell death noted in5-FU-R cells in comparison to 5-FU sensitive cells after5-FU treatment.This resistant cell line overexpressed anti-apoptotic[e.g.,AKT,nuclear factorκB,FLICE-like inhibitory protein),DNA repair(e.g.,DNA polymerase beta(POL-β),DNA polymerase eta(POLH),protein Flap endonuclease 1(FEN1),DNA damage-binding protein 2(DDB2)]and 5-FU-resistance proteins(thymidylate synthase)but under expressed pro-apoptotic proteins(e.g.,DAB2,CK1)in comparison to the parental cells.Increased genotoxicity and apoptosis were observed in resistant cells after combined application of BCNU and Res in comparison to untreated or parental cells.BCNU increased the sensitivity to Res of 5-FU resistant cells compared with parental cells.Fifty percent cell death were noted in parental cells when 18μmol/L of Res was associated with fixed concentration(20μmol/L)of BCNU,but a much lower concentration of Res(8μmol/L)was needed to achieve the same effect in 5-FU resistant cells.Interestingly,increased levels of adenomatous polyposis coli and decreased levels POL-β,POLH,FEN1 and DDB2 were noted after the same combined treatment in resistant cells.CONCLUSION:BCNU combined with Res exerts a synergistic effect that may prove useful for the treatment of colon cancer and to overcome drug resistance.
文摘An energetic salt of bis（l,5-diamino-lH-tetrazolium）3,3＂-bis（nitramino）-4, 4x-azo- furazan （C6H10N2206） was synthesized with the total yield of 61.7% by using 3,4-diaminofurazan （DAF） as the starting material. The structure of the title compound was confirmed by NMR, IR, elemental analysis and single-crystal X-ray diffraction. It crystallizes in orthorhombic, space group P21/c with a = 10.739（2）, b = 6.4765（12）, c = 14.138（3） A, fl= 108.787（3）°, V= 930.9（3） A3, Z = 1, Mr= 486.36, Dc = 1.735 g.cm3, μ= 0.15 mm-1, F（000） = 496, R = 0.042 and wR = 0.121. The thermal stability was analyzed by subsequently differential scanning calorimetry （DSC）. And the enthalpy of formation and detonation was calculated theoretically, showing the first decomposition temperature was 142.1℃, the enthalpy of formation was 1614.23 kJ.mol1 and the detonation velocity and detonation pressure were 8.781 km.s-1 and 30.7 GPa, respectively.
文摘The title compound 1,4-bis(benztriazol-1-ylmethyl)-2,4,5,6-trimethylbenzene crys- tallizes in the monoclinic system, space group Pbca with a = 9.842(5), b = 9.455(5), c = 22.165(12) ?, V = 2062.6(18) ?3, Dc = 1.277 g/cm3, Z = 4, C24H24N6, Mr = 396.49, μ(MoKa) = 0.079 mm-1 and F(000) = 840. The structure was refined to R = 0.0662 and wR = 0.1891 for 1163 observed reflections (I > 2σ(I)). The title molecule has trans-conformation about the central phenyl ring. The zigzag-like molecules are connected by face-to-face π…π stacking to form an infinite 2D layer.
文摘Reaction of 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-thioxo-1,2-dihydropyridine-3-carbonitrile) (1) with methyl iodide afforded the 4,4’-(1,4-phenylene)bis(5-acetyl-6-methyl-2-(methylthio)nicotinonitrile) (2). The reaction of 2 with hydrazine hydrate followed by diazotization reaction af-forded the 1,1’-(1,4-phenylenebis(3-amino-6-methyl-1H-pyrazolo[3,4-b]pyridine-4,5-diyl))bis(e-than-1-one) (3) and 1,1’-(1,4-phenylenebis(3-(chlorodiazenyl)-6-methyl-1H-pyrazolo[3,4-b]-pyridine-4,5-diyl))bis(ethan-1-one) (4) respectively. On the other hand, reaction of 4 with malononitrile, 2-cyanoethanethioamide, ethyl acetoacetate, acetyl acetone, ethyl benzoylacetate, diethylmalonate, ethyl cyanoacetate and phenacylbromide aiming to build up pyrazolotriazine or pyrazole ring on the ring system of 4. Structures of all newly synthesized heterocyclic compounds in the present study were confirmed by considering the data of IR, 1H NMR, mass spectra as well as that of elemental analyses.
