EFFECT OF HALOALLYLAMINES ON POLYAMINE OXIDASE ACTIVITY AND SPERMINE LEVELS IN ASCARIS-SUUM

In parasitic nematodes the rate-limiting step in the polyamine interco nversion pathway is catalysed by polyamine oxidase. MDL 72527, the spe cific inhibitor of mammalian polyamine oxidase, had no effect on the A scaris suum enzyme, whereas its activity was inhibited in a time-depen dent manner by the haloallylamine MDL 72145, originally designed as a specific inhibitor of monoamine oxidase A and B. The dissociation cons tant (K-i) was found to be 0.9 mu M and the enzyme half-life under sat uration conditions (t(50)) was determined to be 0.8 min. Incubation of A. suum in vitro in the presence of 50 mu M MDL 72145 for 6 h resulte d in a decrease in polyamine oxidase activity to about 20% of the cont rol value, and spermine concentrations simultaneously increased about 200%. Both results suggest that MDL 72145 might be a chemical lead com pound for the design of new chemotherapeutic agents against nematode i nfections.