Dihydro-Imidazo Phenanthridinium (DIP)-based DNA Binding Agents with Tuneable Structures and Biological Activity

• Main Author: Smith, Louise Victoria
• Published: University of Glasgow 2006
• Subjects: 615
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484912

A new class ofphenanthridinium derivative (DIP) has been isolated from the reaction of 2-bromoethyl-phenanthridinium bromide with a range of primary amines in excellent yields. The reaction has been used to create a large library of compounds which have been tested for DNA affinity by Isothermal Titration Calorimetry (ITe), and cytotoxicity on ovari8J.J. cancer cell line A2780 using a tetrazolium dye-based microtitration (MTT) assay. The framework was found to intercalate with DNA in the range of 104 M'l, and to have varying toxicity dependent upon the functionality, in particular the hydrophobicity, of the DIP tested. In several cases some DiP molecules were shown to be more active on cancer cell lines than the commercially used cisplatin. Also, it has been established that DIP is significantly more active on some cisplatin resistant cell lines. These interesting results, combined with interesting solution studies, show the DIP framework to be a useful tool for the synthesis ofanti-cancer agents, DNA binders, and molecular devices.