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Dihydroimidazophenanthridinium (DIP)-based DNA binding agents with tuneable structures and biological activity.

Louise V Smith·Alexis D C Parenty·Kevin M Guthrie·Jane Plumb·Robert Brown·Leroy Cronin
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Abstract

We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs) with large structural diversity (1-29) using a "one-pot" approach. The DNA binding constants of DIPs range from 2x10(4) to 1.3x10(5) M(-1), and the free energies for binding range from -5.9 to -6.40 kcal mol(-1). Viscosity measurements demonstrated that the binding of the compounds caused DNA lengthening, thus signifying binding by intercalation. The cytotoxicities of the compounds were determined by tetrazolium dye-based microtitration assays and showed a large range of values (0.09-11.7 microM). Preliminary molecular modelling studies of the DNA-DIP interactions suggested that the DIP moieties can interact with DNA by intercalation, and some R groups might facilitate binding by minor-groove binding. The results provide insight into how to design biologically active DNA binding agents that can interact in these ways.

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Cell Line, TumorCell ProliferationDNAHumansHydrophobic and Hydrophilic InteractionsModels, MolecularMolecular StructurePhenanthridinesJournal ArticleResearch Support, Non-U.S. Gov't

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Louise V Smith, Alexis D C Parenty, Kevin M Guthrie, Jane Plumb, Robert Brown, Leroy Cronin. 2006. Dihydroimidazophenanthridinium (DIP)-based DNA binding agents with tuneable structures and biological activity.. https://doi.org/10.1002/cbic.200600205

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