Research On Interaction Of Novel Bisnaphthalimide Derivatives With DNA

Naphthalimide derivatives acted on DNA are a class of organic compounds known to have wide-ranging biological activities, such as antitumor, antiviral, chemosensors and fluorescence probe, etc. Since the promising pharmacological activity and ease of synthesis the naphthalimides have attracted the attention of many researchers. However, there are few papers reported on the linkers of bisnaphthalimide derivatives with DNA. The study mainly discussed the interaction between DNA and a series of novel bisnaphthalimide derivatives linked by different alkyl-isothiourea/thiourea cation, which contributed to design and development new class of more efficient and special naphthalimides and their conjugates.The interaction of novel naphthalimide derivatives(MN2-MN6, DN2-DN6, AITHN, BITHN, PITHN, PyITHN, DNT6) with DNA were investigated by UV absorption spectra, fluorescence spectra and circular dichroism spectra, etc. The results showed as follows:the binding between mononaphthalimide derivatives(MN2～MN6) and DNA was weaker than bisnaphthalimides(DN2-DN6). It was suggested that the intercalation and electrostatic binding should be the two major modes for interaction between naphthalimide derivatives and DNA. The strength of intercalation was related to the length and the substituent of linker, and the intercalating ability of DN6and AITHN were stronger than other compounds. Since the longer of the alkyl-isothiourea cation, or the smaller of the substituent’s space, the more flexible of the compounds, which was helpful to transform the best structure of compounds. While the electrostatic binding was only dependent on the charge of compounds. The strength of electrostatic binding were different from each other as a result of being influenced by many factors, such as temperature, pH, etc.Meanwhile, the effect of bisnaphthalimide derivatives on the growth of cell were evaluated using MTT method, and the inhibition activity of DNA topoisomerase I was studied by agarose gel electrophoresis. The results showed that the longer of the alkyl-isothiourea cation linkers, the stronger of inhibition on cell’s growth, that is DN6>DN5>DN4>DN3>DN2. The bisnaphthalimide derivatives with same length linker and different kinds of substituents (AITHN, BITHN, PITHN, PyITHN, DN6, DNT6) also showed inhibition against different cell lines, especially DN6and AITHN, which indicated the compound with small substituent had weaker inhibition. In addition, bisnaphthalimides couldn’t form a ternary complex with DNA and topoisomerase I, which was suggested that the bisnaphthalimides showed no inhibition to DNA topoisomerase I.