Inhibition of superoxide dismutase from Ascaris suum by benzimidazoles and synthesized pyrimidine and glycine derivatives

Pharmacology. 1996 Jan;52(1):61-8. doi: 10.1159/000139362.

Abstract

Copper-zinc superoxide dismutase was purified from Ascaris suum (Nematoda). Four benzimidazole derivatives, six recently synthesized pyrimidine derivatives and eleven recently synthesized glycine derivatives were shown to inhibit: (1) purified extracts of A. suum superoxide dismutase; (2) superoxide dismutase from host liver, and (3) purified extracts of superoxide dismutase from living A. suum incubated in the presence of these drugs. Thiabendazole compounds, with a documented effect against helminth parasites, were found to affect the superoxide dismutase. The inhibitory effects of some pyrimidine and glycine derivatives were higher than those of benzimidazoles, and the pyrimidine compounds failed to inhibit the host's enzyme. These derivatives are candidate anthelmintics, acting as inhibitors of certain metalloenzymes in parasites.

MeSH terms

  • Analysis of Variance
  • Animals
  • Anthelmintics / chemical synthesis
  • Anthelmintics / pharmacology*
  • Ascaris suum / enzymology*
  • Benzimidazoles / metabolism
  • Benzimidazoles / pharmacology*
  • Copper / metabolism
  • Electrophoresis, Polyacrylamide Gel
  • Glycine / analogs & derivatives
  • Glycine / metabolism
  • Glycine / pharmacology*
  • Liver / drug effects
  • Liver / enzymology
  • Pyrimidines / metabolism
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • Superoxide Dismutase / antagonists & inhibitors*
  • Superoxide Dismutase / isolation & purification
  • Swine
  • Zinc / metabolism

Substances

  • Anthelmintics
  • Benzimidazoles
  • Pyrimidines
  • Copper
  • Superoxide Dismutase
  • Zinc
  • Glycine