Novel antihelmintic activity of tinidazole coordination compounds. Relevance of the metal ion and structural properties

Abstract

The in vitro and in vivo antihelmintic activity of cobalt(II), copper(II) and zinc(II) coordination compounds of tinidazole (tnz) were investigated in cultivated spotted rose snapper, infested with dactylogyrid monogeneans. The tinidazole coordination compounds [Co(tnz)₂Cl₂], [Co(tnz)₂Br₂], [Cu(tnz)₂Cl₂], [Cu(tnz)₂Br₂], [Zn(tnz)₂Cl₂] and [Zn(tnz)₂Br₂] were synthesized and spectroscopically characterized. Their molecular structures were determined by their single crystal X-ray diffraction. The metal ions presented distorted tetrahedral geometries, with an intramolecular bifurcated lone pair SO⋯π, from the sulfone group with the imidazolic ring, which contributed to the stability of the compounds in solid state and in solution. Adults of dactylogyrids were exposed in vitro to tinidazole and its coordination compounds. The effective median concentrations of copper(II) coordination compounds were lower than those of cobalt(II) and zinc(II), tnz showed no activity. In vivo oral intubation tests were carried out with [Cu(tnz)₂Br₂], [Zn(tnz)₂Br₂] and tnz on snappers infected with dactylogyrids, where the copper(II) compound showed better activity. The absorption and distribution assessment for the [Cu(tnz)₂Br₂], showed that copper concentrations in liver were significantly higher than in blood and gills, indicating bioaccumulation in this organ. In vivo baths of [Cu(tnz)₂Br₂] at 25mg/L showed an effective (95% at 8h) antihelmintic effect, while [Zn(tnz)₂Br₂] had low antihelmintic efficacy. This study indicates that [Cu(tnz)₂Br₂] has an effective antihelmintic activity towards dactylogyrids monogeneans affecting cultivated spotted red snapper.

Keywords: Antihelmintic activity; Ectoparasites; Metal ions; Snappers; Tinidazole coordination compounds.