| Autor: |
Smith LV; WestCHEM Department of Chemistry, Joseph Black Building, University of Glasgow, University Avenue, Glasgow, G12 8QQ, UK., Parenty AD, Guthrie KM, Plumb J, Brown R, Cronin L |
| Jazyk: |
angličtina |
| Zdroj: |
Chembiochem : a European journal of chemical biology [Chembiochem] 2006 Nov; Vol. 7 (11), pp. 1757-63. |
| DOI: |
10.1002/cbic.200600205 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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