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
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
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.
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.
