Hoechst 33258, distamycin, and netropsin are among a number of compounds that bind in the minor groove of DNA

number of compounds that bind in the minor groove of DNA and exhibit various degree of antitumour activity. Several high resolution crystal and NMR structures have been determined for these ligands bound to short oligonucleotides and provide valuable insights into the details of their interaction. The Hoechst 33258 is bound in the minor groove, with the planar benzimidazole groups oriented parallel to the groove direction and each inner-facing nitrogen atom hydrogen bonding in a bifurcated manner to a pair of adjacent hydrogen bond donors on the edge of the AT base pairs of DNA. The structure of the bound drug shows that the bulky piperazine ring is located in a GC region, with the minor groove observed to be wider at this sequence. The spectroscopic characteristics of Hoechst 33258 family of ligands have brought them into wide use as DNA fluorophores, but several have also shown potent activity against a number of microorganisms that lead to AIDS-related opportunistic infections, as well as exhibiting cytotoxic activity. In the course of our investigations of minor groove binding drugs, we reported a cytotoxicity and DNA-binding ability of carbamate derivatives of Hoechst 33258 with chloroalkyl and bromoalkyl moieties (Fig. 1).