Synthesis And Biological Evaluation Of DNA-targeted Drugs Containing Indole Or Isoquinoline Groups

According the design thought of molecular hybridization, this article choose indole or isoquinoline as pharmacophores to decorate different DNA intercalators to design and synthesis three novel series DNA-targeted anticancer drugs. Their molecular structures were confirmed, and their spectral properties combining with DNA and anti-tumor abilities were evaluatd.Based on the bioactivity of 9,10-phenanthrenequione and the anti-tumor effect of the indole derivatives,6 novel phenanthro[9,10-d]imidazole derivatives containing indole groups were synthesized. The structures of the new compounds were testified by MS,1HNMR, 13CNMR and X-ray diffraction. The new compounds could combine with DNA causing the change of double helix structure, which were evaluated by UV-vis spectra, Fluroresence spectra, CD spectra, viscosity assay and so on. The inhibitory activity of tumor cells in vitro showed that they had excellent inhibition activity against MCF-7and BGC-823 cells.4-bromine-1,8-naphthalene anhydride was decorated by isoquinoline as pharmacophores to synthesis the novel naphthalene derivatives as DNA-targeted anti-tumor drugs. The compounds’structures were proven by MS,1HNMR,13CNMR. The spectra data of UV-vis, Fluroresence, CD and the result of viscosity assay indicated that the new compounds showed significant binding abilities with DNA, which could cause the conformation change of DNA and the relaxation of DNA double helix structure. The inhibitory activity of tumor cells in vitro implied that the compounds had remarkable inhibition activity against MCF-7and BGC-823 cells.Depend on the foundation that the increase of conjugate area could improve the ability of DNA binding agents,4 novel N-substituted-imidaznpahthalimide derivatives had been synthesized. Their structures were verified by MS,1HNMR,13CNMR. The results of UV-Vis, fluorescence, CD spectra, ion effects and viscosity assay illustrated that compounds could embedding into DNA base pairs. MTT colorimetric method as used to testify the compounds’ inhibitory activity of tumor cells and the result manifested that all the compounds has prominent inhibitory activity. In particular, Z2 exhibited the best biological abilities with IC50 values against BGC-823 was 8.20μM.