Comparative effects of anthelmintics on c-MDH from Molinema dessetae (Nematoda: Filarioidea) and from a mammal.

Malate dehydrogenase (MDH) (E.C.1.1.1.37) activity was detected in the filaria Molinema dessetae at a level similar to those found in other filariae. In M. dessetae, the cytoplasmic form (c-MDH) predominated and the study was performed on partially purified fractions. The pH optimum for oxaloacetate reduction was 6.1, with maximal activity at 7811 nmol min-1 mg protein-1, but high concentrations of oxaloacetate inhibited MDH activity. The Km value for oxaloacetate was determined as 22 microM for M. dessetae c-MDH and 33 microM for mammalian c-MDH. Anthelmintic drugs were compared as potential inhibitors of filarial and mammalian c-MDH. Among the compounds evaluated, amocarzine showed a specific inhibitory effect on filarial c-MDH through only at high concentrations. Suramin alone showed an inhibitory effect at low concentrations (Ki = 1.15 microM) but without selective action towards filarial c-MDH. The suramin type of inhibition was found to be competitive. Suramin probably acts on both enzymes in the same manner. Nevertheless, M. dessetae c-MDH is proposed as a suitable enzyme assay model to screen MDH inhibitors as potential filaricides.