RESEARCH FOR NEW FILARICIDES BY USING PHOSPHOENOLPYRUVATE-CARBOXYLASEFROM MOLINEMA-DESSETAE (NEMATODA, FILARIOIDEA) AS BIOCHEMICAL TARGET

In the aim to search for new antifilarial drugs, we pro-pose here a st udy of phosphoenolpyruvate-carboxylase (E.C.4.1.1.31) as a therapeutic target. Among some potential inhibitors, compounds Nos. 5 and 9 which are phenoxycyclohexane derivatives were inhibitory with K(i) values r espectively at 122 and 93 muM. The inhibition was found to be noncompe titive. Concerning compound No. 5, the drug concentrations responsible for an enzyme inhibition of 50% were about 2-fold higher than those n ecessary to kill the adult parasite in vitro. Such results suggest the existence of another mechanism involved in this drug's action. Nevert heless, the correlation between in vitro results on adults and enzyme assay appeared clear and validates PEP-carboxylase as a biochemical ta rget which should be investigated using a series of substrate analogue s.