Inhibition of Superoxide Dismutase from Ascaris suum by Benzimidazoles and Synthesized Pyrimidine and Glycine Derivatives

Abstract

Copper-zinc superoxide dismutase was purified from Ascαris 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.

Novel inhibitors to Taenia solium Cu/Zn superoxide dismutase identified by virtual screening

“…In contrast, the rest of the potential sites (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) are much smaller, exposed to solvent, and in many cases, well conserved respect to the human enzyme. In a first stage, the previously generated conformers for each ligand were scanned against all sites on the TsCu/Zn-SOD surface, using 15,000 poses of probe for each conformer.…”

“…As reported by some authors [9], albendazole inhibits microtubule formation in parasite by binding to b-tubulin, however, as shown by Sánchez-Moreno et al [17][18][19], this drug also inhibits SOD enzymes in helmints, but at high concentrations in the case of T. solium, as reported by us [20]. Gómez-Contreras et al [21] reported recently the synthesis of benzo[g]phthalazine derivatives which selectively inhibit Fe-SOD activity and growth of Trypanosoma cruzi.…”

Three- and four-coordinate Ag(I) complexes of crotonate and bis(benzimidazole)-2-oxapropane ligands: syntheses, crystal structures, DNA-binding studies and antioxidant activities

“…The absence of crystal field stabilization for the d 10 monovalent silver cation, coupled with its ability to tolerate a wide range of coordination geometries (with coordination numbers spanning 2-7), leads to considerable variation in the geometry and connectivity of the networks that can be formed when Ag(I) centers act as connectors [14,15]. Their various biological applications have also attracted attention [16].…”

Synthesis, Spectroscopic, and Electrochemical Studies on Some New Copper(II) Complexes Containing 2-{[(Z)-Phenyl (Pyridine-2-yl) Methylidene] Amino}Benzenethiol and Monodentate Ligands

“…Imidazole and its derivatives are very important from a biological point of view [8]; namely, benzimidazole as the 5,6-dimethyl derivative is present in vitamin B 12 and related biomolecules [9] and other benzimidazole compounds have found wide use as anthelmintic agents for both human and veterinary purposes [10]. In addition, it has been reported that several copper complexes with benzimidazole derivatives show inhibitory effects on helminth parasites [11]. Imidazole is also one of the most biologically important ligands.…”