A prototype bioreductive DNA groove binding ligand.
Molecular mechanics calculations have been used to evaluate the potential bioreductive behaviour of several DNA minor groove binding ligands containing quinone/hydroquinone redox systems. The proposed structures are analogues of the Hoechst 33258 molecule with modifications of the benzimidazole rings. Binding energies of simple analogues indicate the reduced forms bind more strongly to the DNA minor groove. N-methylation of the imidazole ring(s) produces structures which can form extended quinone methides. These also show stronger binding in the reduced form and it is speculated that such structures might provide a basis for the design of groove binding ligands which will act as bioreductive alkylating agents.
Haworth
I S
IS
Physical Chemistry Laboratory, Oxford, UK.
Burt
C
C
Gago
F
F
Reynolds
C A
CA
Richards
W G
WG
D001483:Base Sequence; D001665:Binding Sites; D006690:Bisbenzimidazole / Q000031:analogs & derivatives / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D013816:Thermodynamics
D008024:Ligands; D004247:DNA; D006690:Bisbenzimidazole