Synthesis And Biological Evaluation Of DNA-targeted Heterocycle-fused Naphthalene Derivatives

Three series of DNA-targeted compounds based on the restructuring of naphthalimide and benzo[c, d]indol-2(1H)-one were designed and synthesized.Their spectral properties, DNA-binding, anti-tumor and DNA damaging abilities were evaluated.8 novel 2,1,3-thiadiazole fused 1,8-naphthalimide derivatives had been synthesized and the results of UV-Vis spectra, Fluorescence spectra, CD spectra and viscosity measurement all showed that the compounds had good DNA binding ability. S1 binding constant could reach 2.83×105 mol-1·L. The change appeared in the CD spectra of DNA when incubated with S1 and S4 illustrated that the compounds interacted with DNA by the classical intercalating mode, making the positive band increase and the negative band decrease. All the compounds could cleave supercoiled plasmid DNA, especially S3. S1-4, bearing flexible amine side chains, exhibited excellent cytotoxicity to the selected cell lines, especially S1.3 against 7721 cells, the IC50 value of which were as low as 10-7 M.A series of N-substituted benzoyloxy-2,3-dimethylpyrazine fused naphthalimides had been designed and synthesized. Their DNA affinity were investigated by UV-Vis, Fluorescence, CD spectra and viscosity measurement and the results manifested that the compounds had limited intercalation ability. CD spectra of DNA after the adding of N1 and N7 indicated that their intercalating processes were accompanied by certain aggregation. Under radiation, the compounds could damage DNA effectively. N2 and N6 were found to be more sensitive to HL60 cells in inhibitory test, with IC50 values 4.81×10-7 M and 3.08×10-7 M respectively.5 new benzo[c,d]indol-2(1H)-one derivatives were synthesized. Their interaction mode with DNA were studied by UV-Vis spectra, Fluorescence spectra, CD spectra and viscosity measurement. All the results displayed that the compounds could insert to the base pairs of DNA. They had similar DNA photo-damaging ability. NB1 had the highest inhibition activity to the three cell lines, the IC50 values against 7721 and MCF-7 were 2.7×10-7 M and 1.4×10-7 M, respectively. DFT calculation was used to optimize their structures to evaluate the effects of different substitutes on the original structure.