POLYAMINES AS TARGETS FOR THERAPEUTIC INTERVENTION

Polyamines are ubiquitous cell components essential for normal growth. Compounds interfering with polyamine biosynthesis or function have co nsiderable potential for use as therapeutic agents. Inhibitors of orni thine decarboxylase have been shown to be valuable for the treatment o f 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 pot ential 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. Po lyamine analogues, notably those with ethyl or benzyl groups on the te rminal nitrogen atoms, have potent antiproliferative activity and are promising agents for the treatment of cancer. These analogues are tran sported by the polyamine-transport system, and their therapeutic effec ts are less likely to be blocked by the availability of the exogenous polyamines.