The photocleavage abilities of a novel family of compounds, 8-oxo-8%H%-acenaphtho pyrrole-9-carbonitrile and its derivatives(compounds 1—5) were evaluated with M13 mp18 single strand circular DNA. Only compound 1 wit...The photocleavage abilities of a novel family of compounds, 8-oxo-8%H%-acenaphtho pyrrole-9-carbonitrile and its derivatives(compounds 1—5) were evaluated with M13 mp18 single strand circular DNA. Only compound 1 with a diethylamine group could bind to DNA %via% electrostatic attraction and intercalation. At a concentration of 50 μmol/L, it could generate singlet oxygen to cleave circular DNA into linear DNA under the irradiation of long wavelength light(λ>400 nm). The antitumor {ability} of compound 1 was also evaluated in vitro, and its IC_ 50 on HeLa cells was as low as 6.8 μmol/L.展开更多
1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hyd...1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hydride (DIBAL-H) with a novel rearrangement reaction.展开更多
AIM: To investigate the efficacy of moxibustion in ulcerative colitis(UC) rats from morphological, immunological and molecular biological perspectives.METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to ...AIM: To investigate the efficacy of moxibustion in ulcerative colitis(UC) rats from morphological, immunological and molecular biological perspectives.METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group(normal rats, n = 6) and a model replication(MR) group(UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion(9M) group(9 moxa-cone, n = 6), 6-min moxibustion(6M) group(6 moxa-cone, n = 6), 3-min moxibustion(3M) group(3 moxa-cone, n = 6), and a waiting list control(WLC) group(no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin(IL)-8 and IL-10, and expression of Toll-like receptor(TLR)9 aswell as nuclear factor(NF)-κB p65 in colonic tissue were determined by disease activity index(DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively.RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment(3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons(0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons(105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons(0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65).CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats.展开更多
To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA ...To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA were rex;ealed through absorption titration, SYBR Green-DNA melt curve, circular dichroism（CD）, and docking studies. It was identified that some of the compounds could intercalate into DNA along their long axis parallel to the base-pair long axis, making right-handed B form DNA transform to A-like conformation. Their binding potency varied with the different steric hindrance. Their cytotoxicity（IC50） against MCF-7 cells was found to range between 1.3 to 40.9 umol/L by MTT assay. Interestingly, the IC50 values did not show any obvious correlation to their binding constants with DNA. The chromophore with a carboxyl group exhibited the most potency of intercalating DNA and could be the promising precursor for the future intercalator for DNA, while the bromide demonstrated the highest cytotoxic activity in this series of compounds.展开更多
By means of circular dichroism（CD） spectrum coupled with UV-Vis and fluorescence spectra,the binding model of DNA intercalator A1{4-（2-diethylamino-ethylamino）-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile} to ...By means of circular dichroism（CD） spectrum coupled with UV-Vis and fluorescence spectra,the binding model of DNA intercalator A1{4-（2-diethylamino-ethylamino）-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile} to calf thymus（CT） DNA was investigated,depending on the values of R（R is defined as the ratio of the concentration of A1 to CT DNA base pairs） and different outer factors.Molecules A1 were intercalated into the CT DNA base pairs in different orientations in the intercalation pocket at a lower R value（R≤0.20）,while A1 molecules aggregated on the surface of the helix of the CT DNA as the R value increased.The influence of NaCl on the binding was smaller because the electrostatic interaction only provided approximately 16% of the overall free energy of binding.The protonated diethylamine substitution would influence the binding geometry greatly at a low pH value via forming hydrogen bonds with the exposed C=O group on DNA surface.展开更多
文摘The photocleavage abilities of a novel family of compounds, 8-oxo-8%H%-acenaphtho pyrrole-9-carbonitrile and its derivatives(compounds 1—5) were evaluated with M13 mp18 single strand circular DNA. Only compound 1 with a diethylamine group could bind to DNA %via% electrostatic attraction and intercalation. At a concentration of 50 μmol/L, it could generate singlet oxygen to cleave circular DNA into linear DNA under the irradiation of long wavelength light(λ>400 nm). The antitumor {ability} of compound 1 was also evaluated in vitro, and its IC_ 50 on HeLa cells was as low as 6.8 μmol/L.
文摘1,7β- Dimethyl-7α- hydroxy-8aα-carboxymethyl-9β-carbomethoxy-4bα, 5, 6, 7, 8, 8α-hexahydrofluorene lactone(2) is converted to 8, 12-epoxyallogibberic acid methyl ester(4) by the action of diisobutyl aluminum hydride (DIBAL-H) with a novel rearrangement reaction.
基金This study is supported by China National Nattu-al Science Foundation （Project 31040006） and Beijing Natural Science Foundation and Scientific Research Key Program of Beijing Commission of Education （NO. KZ200910020001）.
基金Supported by Scientific and Technological Project of Educational Department of Liaoning Province,China,No.L2011166
文摘AIM: To investigate the efficacy of moxibustion in ulcerative colitis(UC) rats from morphological, immunological and molecular biological perspectives.METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to a blank control group(normal rats, n = 6) and a model replication(MR) group(UC rats, n = 26). A UC model was established by 2,4,6-trinitrobenzenesulfonic acid/dextran sulfate sodium enema. Rats in the MR group were further randomly assigned to a 9-min moxibustion(9M) group(9 moxa-cone, n = 6), 6-min moxibustion(6M) group(6 moxa-cone, n = 6), 3-min moxibustion(3M) group(3 moxa-cone, n = 6), and a waiting list control(WLC) group(no moxibustion treatment, n = 6). Rats in the moxibustion treatment group were treated in 14 sessions over 28 d. Disease activity, local tissue morphology, serum level of interleukin(IL)-8 and IL-10, and expression of Toll-like receptor(TLR)9 aswell as nuclear factor(NF)-κB p65 in colonic tissue were determined by disease activity index(DAI), hematoxylin and eosin staining, electron microscopy, enzyme-linked immunosorbent assay and Western blotting, respectively.RESULTS: DAI was lowest in the 9M group and highest in the WLC group. The differences in DAI between the moxibustion treatment(3M, 6M, 9M) and no treatment groups were significant for all one-to-one comparisons(0.60 ± 0.54 vs 1.20 ± 0.44, 0.60 ± 0.54 vs 1.80 ± 0.45, 0.60 ± 0.54 vs 3.0 ± 0.45, respectively, P < 0.05). Light and electron microscopy showed that the neatness of the glandular arrangement in colonic mucosal epithelia gradually increased in the WLC, 3M, 6M to 9M groups. IL-8 level successively decreased while IL-10 level increased from the WLC to 3M, 6M and 9M groups. The differences among these groups were significant for all comparisons(105.46 ± 8.75 vs 76.61 ± 3.58, 105.46 ± 8.75 vs 69.78 ± 1.87, 105.46 ± 8.75 vs 67.41 ± 1.84, respectively, P < 0.01 for IL-8; and 30.83 ± 1.29 vs 75.64 ± 1.90, 30.83 ± 1.29 vs 80.90 ± 3.16, 30.83 ± 1.29 vs 83.46 ± 2.37, respectively, P < 0.01 for IL-10), except comparison of 6M vs 9M. Expression of TLR9 and NF-κB p65 decreased in order: highest in the WLC group and lowest in the 9M group. In addition, the differences among the WLC, 3M, 6M and 9M groups were significant for all comparisons(0.492 ± 0.026 vs 0.380 ± 0.022, 0.492 ± 0.026 vs 0.355 ± 0.005, 0.492 ± 0.026 vs 0.327 ± 0.015, respectively, P < 0.05 for TLR9; and 0.436 ± 0.041 vs 0.326 ± 0.022, 0.436 ± 0.041 vs 0.293 ± 0.006, 0.436 ± 0.041 vs 0.265 ± 0.017, respectively, P < 0.05 for NF-κB p65).CONCLUSION: Moxibustion repairs damaged colonic mucosa, suppresses serum IL-8, activates serum IL-10 level, and decreases expression of TLR-9 and NF-κB p65 in UC rats.
基金the National Natural Science Foundation of China(No.30772622)
文摘To explore new platform for DNA intercalation and potent antitumor agent, a series of 8-oxo-8H- acenaphtho[1,2-b]pyrrole-9-carboxylic acid esters chromophores has been studied. Their intercalation geometries with DNA were rex;ealed through absorption titration, SYBR Green-DNA melt curve, circular dichroism（CD）, and docking studies. It was identified that some of the compounds could intercalate into DNA along their long axis parallel to the base-pair long axis, making right-handed B form DNA transform to A-like conformation. Their binding potency varied with the different steric hindrance. Their cytotoxicity（IC50） against MCF-7 cells was found to range between 1.3 to 40.9 umol/L by MTT assay. Interestingly, the IC50 values did not show any obvious correlation to their binding constants with DNA. The chromophore with a carboxyl group exhibited the most potency of intercalating DNA and could be the promising precursor for the future intercalator for DNA, while the bromide demonstrated the highest cytotoxic activity in this series of compounds.
基金Supported by National Natural Science Foundation of China(No.30772622)
文摘By means of circular dichroism（CD） spectrum coupled with UV-Vis and fluorescence spectra,the binding model of DNA intercalator A1{4-（2-diethylamino-ethylamino）-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile} to calf thymus（CT） DNA was investigated,depending on the values of R（R is defined as the ratio of the concentration of A1 to CT DNA base pairs） and different outer factors.Molecules A1 were intercalated into the CT DNA base pairs in different orientations in the intercalation pocket at a lower R value（R≤0.20）,while A1 molecules aggregated on the surface of the helix of the CT DNA as the R value increased.The influence of NaCl on the binding was smaller because the electrostatic interaction only provided approximately 16% of the overall free energy of binding.The protonated diethylamine substitution would influence the binding geometry greatly at a low pH value via forming hydrogen bonds with the exposed C=O group on DNA surface.
