title: Comparative effects of anthelmintics on c-MDH from Molinema dessetae (Nematoda: Filarioidea) and from a mammal.
abstract: 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.
authors.affiliation: Biologie et Contrôle des Organismes Parasites, Université de Paris XI, Châtenay-Malabry, France.
authors.forename: P M
authors.initials: PM
authors.lastname: Loiseau
authors.forename: M
authors.initials: M
authors.lastname: Maarouf
authors.forename: P
authors.initials: P
authors.lastname: Gayral
authors.forename: F
authors.initials: F
authors.lastname: Petek
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002412:Cations; D005370:Filarioidea / Q000187:drug effects* / Q000201:enzymology; D006863:Hydrogen-Ion Concentration; D008291:Malate Dehydrogenase / Q000037:antagonists & inhibitors / Q000187:drug effects*; D008322:Mammals; D010071:Oxaloacetates / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D012996:Solutions; D013498:Suramin / Q000494:pharmacology; D013696:Temperature
chemical_list: D000871:Anthelmintics; D002412:Cations; D010071:Oxaloacetates; D010879:Piperazines; D012996:Solutions; D013498:Suramin; C051744:amocarzine; D008291:Malate Dehydrogenase