Interaction of amoscanate with the cyclic AMP-phosphodiesterases from Schistosoma mansoni, Onchocerca volvulus and bovine heart.
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.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000814:Aniline Compounds / Q000494:pharmacology*; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D002147:Calmodulin / Q000378:metabolism; D002417:Cattle; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; D004159:Diphenylamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D017879:Isothiocyanates; D009206:Myocardium / Q000201:enzymology*; D009854:Onchocerca / Q000201:enzymology*; D012550:Schistosoma mansoni / Q000201:enzymology*; D013861:Thiocyanates / Q000494:pharmacology*
D000814:Aniline Compounds; D000871:Anthelmintics; D002147:Calmodulin; D017879:Isothiocyanates; D013861:Thiocyanates; D004159:Diphenylamine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054677:Cyclic Nucleotide Phosphodiesterases, Type 1; C012391:amoscanate