Parasite-specific inhibition of 5'-nucleotidase from Onchocerca volvulus and Dirofilaria immitis by the amoscanate-derivative CGP 8065.
The presence of 5'-nucleotidase was demonstrated in Onchocerca volvulus and Dirofilaria immitis; the bulk of activity was found in the particulate fraction. The enzyme of filarial worms exhibited a broad pH-optimum between 6.4 and 8.0 and substrate specificity for nucleotides compared to glucose-6-phosphate and p-nitrophenyl phosphate. The apparent Km-values for AMP were found to be 0.15 mM and 0.22 mM for the enzyme from O. volvulus and D. immitis, respectively. The activity of 5'-nucleotidase from both filarial worms was effectively inhibited by the filaricidal compound CGP 8065, a dithiocarbamate-derivative of amoscanate, whereas the 5'-nucleotidase from rat liver was not affected. The parasite-specific inhibition by CGP 8065 was found to be reversible and to be competitive with respect to the substrate AMP. The inhibition constants were calculated to be 24 microM and 8 microM for the enzyme from O. volvulus and D. immitis, respectively.
Walter
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Albiez
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D015720:5'-Nucleotidase; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D004183:Dirofilaria immitis / Q000187:drug effects / Q000201:enzymology*; D004285:Dogs; D005370:Filarioidea / Q000201:enzymology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009708:Nucleotidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009854:Onchocerca / Q000187:drug effects / Q000201:enzymology*; D013859:Thiocarbamates / Q000494:pharmacology*
D013859:Thiocarbamates; D000249:Adenosine Monophosphate; C045009:CGP 8065; D009708:Nucleotidases; D015720:5'-Nucleotidase