Synthesis, DNA Binding And Biological Activity Of Comb-like DNA Intercalators

We designed,synthesized two of comb-like DNA intercalators combined by naphthalimide and naphthalene groups.These compounds were charazterized by NMR,IR and MS.The anti-tumor activity of the compounds were tested by the MTT method in vitro.The effect of the compounds in tumor cells was studied by apoptosis and cell cycle experiments,and the localization of the compounds in tumor cells was observed by laser confocal microscopy.Furthermore,their DNA binding abilities was evaluated by UV-vis spectra,viscosity.Firstly,we synthesized 8 intercalators with different amino acid linkers.These compounds were charazterized by NMR,IR and MS.According to the results of UV-Vis spectra and viscosity experiments,these compounds were shown good DNA binding ability.The binding constant K_b of compounds 5a-5h were 1.153×105 M^-1,1.968×105 M^-1,1.718×105 M^-1,3.87×105 M^-1,2.933×105 M^-1,1.269×105 M^-1,and0.957×105 M^-1,respectively.According to the results of MTT assay in vitro,most of compounds inhibited the growth various human tumor cells tested in our experiments.Among these compounds,5a,5c,and 5f were shown better cytoto-xicity activities than 5-fluorouracil.Therefor,5a,5c,and 5f were used as model compound to study by apoptosis and cell cycle experiments in BGC823 cells.It was found that the early apoptotic effect of the compound in the cell was particularly obvious.To study the subcellular localization of the compounds,Hep G2 tumor cell line was selected for compound staining experiments.According to the experiment results,compounds 5a-5h were distributed both in the nucleus and cytoplasm,which indicating the synthesized intercalators binding with the nuclei of tumor cell.Secondly,we further synthesized 4 intercalators with different chain length.These compounds were also charazterized by NMR,IR and MS.According to the results of UV-Vis spectra and viscosity experiments,these compounds were illustrated could intercate into DNA base pairs.The binding constant K_b of compounds 9c-11c were 7.157×105M^-1,5.664×105M^-1,and 0.827×105M^-1,respect-ively.The interaction between the compound and DNA is related to the chain length and solubility in phosphate buffer.According to the results of MTT assay in vitro,these compounds also inhibited the growth various human tumor cells tested in our experiments and were shown better cytoto-xicity activities than 5-fluorouracil.Therefor,10c and 11c were used as model compound to study by apoptosis and cell cycle experiments in BGC823 cells.It was also found that the early apoptotic effect of the compound in the cell was particularly obvious.To further study the subcellular localization of the compounds,Hep G2 tumor cell line was likely selected for compound staining experiments.According to the experiment results,compounds 9c-11c were distributed both in the nucleus and cytoplasm,which indicating the synthesized intercalators binding with the nuclei of tumor cell.