EPOXYETHANE- ETHYNESULFONAMIDES WITH ANTIFILARIAL ACTIVITIES - DEGRADATION KINETICS AND INHIBITORY EFFECT ON FILARIAL MALATE-DEHYDROGENASE AND LACTATE-DEHYDROGENASE/

Some epoxyethane-/ethynesulfonamides had shown strong filaricidal acti vity with inconstant reproducibility as a result of a lack of stabilit y in aqueous solution. The degradation in hydroxylic and aprotic solut ions of two epoxyethanesulfonamides and one ethynesulfonamide was inve stigated using TLC, HPLC, GC and mass spectrometry. For both epoxydes, the degradation rate followed first-order kinetics and was more rapid in hydroxylic than in aprotic solutions. The degradation increased wi th the temperature whereas it was not modified with and without light exposure. Four kinds of degradation products were found: the first one involved the oxidation of the epoxyde bond, the second the breaking o f the N-S bond, the third a desulfonation product and the fourth was n ot identified. In contrast, the stability of ethynesulfonamide was bet ter than those of epoxyethanesulfonamide. These results suggest that e poxyethanesulfonamides should be kept at + 4 degrees C before being in jected to animals during the study of biological activity. Since epoxy de compounds are known to have inhibitory effects on parasite energy m etabolism enzymes, the compounds were evaluated on two major filarial enzymes: lactate dehydrogenase (LDH) and cytoplasmic malate dehydrogen ase (MDH). Both epoxyethanesulfonamides showed only a slight inhibitor y effect on filarial LDH and MDH confirming the evidence that the main mode of action of these compounds remains to discover. Moreover, ethy nesulfonamide and the degradation products of both epoxyethanesulfonam ides had no effect on LDH and MDH.