The Azinomycins, Discovery, Synthesis and DNA binding Studies

Nature is a rich source of antitumour agents that can act as a paradigm for the development of synthetic agents that retain the biological activity of the natural product but are targeted to the tumor, have increased bioavailability or are simply prodrug forms that are inactive until administered. Examples of potent antitumour antibiotics that interact with DNA include CC-1065 and the duocarmycins, ecteinascidin 743 and rebeccamycin.

The azinomycins A (1) and B (2) (Fig. 24.1) and the truncated analogue 3 represent novel structures that have been extensively explored from a synthetic viewpoint, bot for which studies of structure-activity relationships from a DNA binding and biological viewpoint have been few and widely spaced chronologically. In this chapter we aim to bring together the details of the isolation, synthesis, structural, and DNA-binding studies of the azinomycins, to generate a starting point from which to begin to understand the properties of these natural products that could lead to new, therapeutically relevant compounds.