Synthesis, characterization and medical efficacy (hepatoprotective and antioxidative) of albendazole-based copper(II) complexes - an experimental and theoretical approach

A series of albendazole-based copper(II) complexes with different counter anions, [Cu(Albz)(H2O)(2)](ClO4)(2) (1), [Cu(Albz)(2)(Cl)]Cl2H(2)O (2), [Cu(Albz)(2)(NO3)](NO3) (3), and [Cu-2(Albz)(2)(-SO4)(2)(H2O)(2)] (4) (Albz=albendazole), have been synthesized and characterized. Their structures and properties were characterized by elemental analysis, thermal analysis (TGA, DTG and DTA), IR, UV-vis and ESR spectroscopies, cyclic voltammetry, electrical molar conductivity, and magnetic moment measurements. A square-planar geometry is proposed for 1, whereas the five-coordinate copper(II) complexes 2, 3, and 4 have a square pyramidal geometry. Theoretical calculations (DFT) using B3LYP/6-311+G(d,p) level of theory corroborated the experimental results to investigate both the drug Albz and its copper(II) complex, 1. The hepatoprotective and antioxidative efficacy of Albz and 1-4 were evaluated against carbon tetrachloride-induced acute hepatotoxicity in rats. Hepatotoxicity in experimental rats was evidenced by significant decrease in the antioxidant enzyme activities (SOD, GSH-S-transfers, and GSH-Rd levels). The results have strong impact for designing anticancer drugs, combined with their potential cytotoxic and antioxidant activities, which can be targeted selectively against cancer cells and increase their therapeutic index and advantages over other anticancer drugs. The DNA cleavage studies of Albz and its copper(II) complexes using genomic DNA indicated that Albz has no role in cleavage of DNA, and only 1 played a marked role in the DNA cleavage without any external additives.