Polyamines as targets for therapeutic intervention

Abstract

Polyamines are ubiquitous cell components essential for normal growth. Compounds interfering with polyamine biosynthesis or function have considerable potential for use as therapeutic agents. Inhibitors of ornithine decarboxylase have been shown to be valuable for the treatment of diseases caused by parasitic protozoa, most notably African sleeping sickness. They may also be useful chemopreventive and antineoplastic agents. Inhibitors of S-adenosylmethionine decarboxylase also have potential as treatments of these diseases. Protocols minimizing uptake of exogenous polyamines via the polyamine-transport system will probably be needed for the full potential of the inhibitors to be realized. Polyamine analogues, notably those with ethyl or benzyl groups on the terminal nitrogen atoms, have potent antiproliferative activity and are promising agents for the treatment of cancer. These analogues are transported by the polyamine-transport system, and their therapeutic effects are less likely to be blocked by the availability of the exogenous polyamines.