Pro-oxidant and antiproliferative effects of the 1,3,4-thiadiazole–based Schiff base and its metal complexes

Abstract

Adverse biological activities of Schiff base (SB) derivatives are well known. In this study, the ligand and its metal complexes have been synthesized and characterized by IR, 1H-NMR spectra, elemental analyses, magnetic susceptibility, UV-Vis spectra, and thermogravimetry/differential thermal analysis. From the elemental analyses data, the complexes were proposed to have the general formula [Mn(L)2(H2O)2], [Co(L)2(H2O)2], and [Ni2(L)(H2O)4(Cl)3]. From the magnetic moment and UV-Vis spectra data, it was found that the geometrical structures of these complexes are octahedral. In the in vivo experiment, adult male rats were injected subcutaneously with a new SB (L) and its [Mn(L)2(H2O)2], [Co(L)2(H2O)2], and [Ni2(L)(H2O)4(Cl)3] complexes (25 mg/kg body weight) and were then sacrificed 16 days later. Effects of these compounds on serum antioxidant vitamins (i.e., vitamins A, E, and C) and malondialdehyde (MDA) levels were measured in blood serum, liver, and kidney tissues. In an in vitro experiment, antiproliferative effects of these compounds were assessed on the human breast carcinoma MCF-7 and murine leukemia L1210 cell lines. Serum MDA and vitamins A, E, and C levels did not change by the treatments. However, in the kidney and liver tissues, MDA levels were higher, whereas vitamin levels were lower in treatment groups, compared to the control group. All compounds inhibited cell proliferation of MCF-7 and L1210 cancer cell lines in a dose- and time-dependent manner. In conclusion, SB derivatives tested in the current study induced oxidative stress in vivo and exhibited anti-proliferative effects in an in vitro culture system.