Interaction of amoscanate with the cyclic AMP-phosphodiesterases from Schistosoma mansoni, Onchocerca volvulus and bovine heart.

Abstract

The anthelmintic compounds amoscanate (4-isothiocyanato-4'-nitrodiphenylamine) and its derivatives CGP 6140 and CGP 8045 are potent inhibitors of the activities of cyclic AMP-phosphodiesterases from schistosomal and filarial worms as well as from both the calmodulin-dependent and the -independent enzyme of bovine heart. As shown for CGP 8045 the type of inhibition is non-competitive with respect to the substrate and the inhibition constants were determined to be in the range of 50 micrograms/ml for the enzymes of parasites and mammalian. It is proposed that the inhibition of cyclic AMP-phosphodiesterase-activity by amoscanate and derivatives - resulting in accumulation of cyclic AMP - might subsequently lead to disturbances in the regulation of metabolic areas like glycogen metabolism which are controlled by cyclic AMP-dependent protein kinases.