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

Smith, L.V., Parenty, A.D.C., Guthrie, K.M., Plumb, J., Brown, R. and Cronin, L. (2006) Dihydroimidazophenanthridinium(DIP)-based DNA binding agents with tuneable structures and biological activity. ChemBioChem, 7(11), pp. 1757-1763. (doi: 10.1002/cbic.200600205)

Abstract

We have synthesised a library of dihydroimidazophenanthridinium cations (DIPs) with large structural diversity (<b>1-29</b>) using a one-pot approach. The DNA binding constants of DIPs range from 2×10⁴ to 1.3×10⁵ 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 M). 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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Parenty, Mr Alexis and Cronin, Miss Lauren
• Authors: Smith, L.V., Parenty, A.D.C., Guthrie, K.M., Plumb, J., Brown, R., and Cronin, L.
• Subjects: Q Science > QH Natural history > QH426 Genetics; Q Science > QH Natural history > QH345 Biochemistry; Q Science > QP Physiology
• College/School: College of Science and Engineering > School of Chemistry; University Centres > Glasgow Materials Research Initiative
• Journal Name: ChemBioChem
• ISSN: 1439-4227