DNA Minor Groove Binder Hoechst 33258 and its Analogues: a Review

Abstract

The synthetic dye Hoechst 33258, i.e. 2-(4-hydroxyphenyl)-5-[5-(4-methylpiperazine-1-yl) benzimidazo-2-yl]-benzimidazole is known to bind strongly to the minor groove of double-stranded B-DNA with specificity for AT-rich sequences. It is an N-methyl piperazine derivative with two benzimidazole groups and one phenol group. It is the best known of the bis-benzimidazole family of minor groove binders. Since the early 1970s, Hoechst 33258 has been widely used as a fluorescent DNA stain because it has ready access into cells. Hoechst derivatives are used in plant cell biology for chromosome and nuclear staining, analysis of nuclear DNA content values (flow cytometry), analysis of plant chromosomes, etc. Hoechst analogues also find uses as radioprotectors and topoisomerase inhibitors. This family of drugs therefore provides a starting point for rational drug design. It is also a good model system with which to investigate the molecular basis for DNA sequence recognition and binding. The existing literature on this family of drugs is reviewed here