Synthesis And Biological Evaluation Of DNA-targeted Anticancer Agents Of Naphthalene Carboxamide Derivatives Containing1,2,3-Triazole

We designed, synthesized three series of DNA-targeted anticancer agents by modifying classical matrix1,8-naphthalimide and benzo[c, d]indol-2(1H)-one.Their structures were proved by TOF MS and1HNMR. By UV-vis spectra, Fluroresence spectra, CD spectra and viscosity assay to evaluate their DNA binding abilities. And we employed MTT assay to futher evaluate their anti-tumor activity.4novel naphthalene lactam derivatives containing1,2,3-triazol were successfully synthesized. All compounds were verified by1HNMR and TOF MS. The results of UV-Vis spectra, fluorescence spectra, CD spectra and viscosity assay showed that these compounds could intercate into DNA base pairs and make DNA conformation changed. All compounds exhibited excellent inhibition of cancer cell proliferation, the IC50value could amount to10-6M, such as T1that the IC50value against MCF-7and Hela were8.29μM and9.23μM, respectively.1,8-naphthalimide was choosed as starting material, we modified naphthalimide at4site by introducing1,2,3-triazol and benzothiazole via "Click Chemistry", then finally got6novel "non-fused" naphthalimide derivatives.The changes of UV-Vis spectra and enhancement of flurorensence Intensity proved that they could intercalate into the DNA effectively.CD spectra results indicated M3could turn the conformation of DNA from B to A-like, M4could change the B-DNA to C-DNA, and M5,M6stabilized the B-DNA. According to the bioactivities assays, Most of compounds showed improved cytotoxicity, in particular M3and M4, the IC50values against MCF-7and Hela were0.35μM、0.12μM and0.66μM、0.19μM, respectively. And both of them were more cytotoxicity against MCF-7and Hela than7721.On account of bioactivity of triazole and benzothiazole, we designed and synthesized a series of naphthalimide derivatives. Their structures were verified by1HNMR and TOF MS.All compounds intercalated into the base pairs of DNA and transformed the B-DNA to A-DNA monitored by spectroscopy techniques and viscosity measurement. MTT assay showed the activity of inhibition of cell growth was excellent, such as compound F1against MCF-7that the potent was2.58fold higher than amonafide, F3against MCF-7and Hela were1.57and2.06fold higher than amonafide.