Anti-toxoplasma activity and DNA-binding of copper(II) and zinc(II) coordination compounds with 5-nitroimidazole-based ligands

Abstract

Tetrahedral copper(II) and zinc(II) coordination compounds from 5-nitroimidazole derivatives, viz. 1-(2-chloroethyl)-2-methyl-5-nitroimidazole (cenz) and ornidazole 1-(3-chloro-2-hydroxypropyl)-2-methyl-5-nitroimidazole (onz), were synthesized and spectroscopically characterized. Their molecular structures were determined by X-ray diffraction studies. The complexes [Cu(onz)₂X₂], [Zn(onz)₂X₂], [Cu(cenz)₂X₂] and [Zn(cenz)₂X₂] (X⁻ = Cl, Br), are stable in solution and exhibit positive LogD_7.4 values that are in the range for molecules capable of crossing the cell membrane via passive difussion. Their biological activity against Toxoplasma gondi was investigated, and IC₅₀ and lethal dose (LD₅₀) values were determined. The ornidazole copper(II) compounds showed very good antiparasitic activity in its tachyzoite morphology. The interaction of the coordination compounds with DNA was examined by circular dichroism, fluorescence (using intercalating ethidium bromide and minor groove binding Hoechst 33258) and UV–Vis spectroscopy. The copper(II) compounds interact with the minor groove of the biomolecule, whereas weaker electrostatic interactions take place with the zinc(II) compounds. The spectroscopic data achieved for the two series of complexes (namely with copper(II) and zinc(II) as metal center) agree with the respective DNA-damage features observed by gel electrophoresis.

Graphical abstract