Iron, copper and manganese complexes with in vitro superoxide dismutase and/or catalase activities that keep Saccharomyces cerevisiae cells alive under severe oxidative stress

摘要

Due to their aerobic lifestyle, eukaryotic organisms have evolved different strategies to overcome oxidative stress. The recruitment of some specific metalloenzymes such as superoxide dismutases (SODs) and catalases (CATs) is of great importance for eliminating harmful reactive oxygen species (hydrogen peroxide and superoxide anion). Using the ligand HPCINOL {1-[bis(pyridin-2-ylmethyl)amino]-3-chloropropan-2-ol}, we have synthesized three coordination compounds containing iron(III), copper(II), and manganese(II) ions, which are also present in the active site of the above-noted metalloenzymes. These compounds were evaluated as SOD and CAT mimetics. The manganese and iron compounds showed both SOD and CAT activities, while copper showed only SOD activity. The copper and manganese in vitro SOD activities are very similar (IC50 similar to 0.4 mu mol dm(-3)) and about 70-fold higher than those of iron. The manganese compound showed CAT activity higher than that of the iron species. Analyzing their capacity to protect Saccharomyces cerevisiae cells against oxidative stress (H2O2 and the O-2(center dot-) radical), we observed that all compounds act as antioxidants, increasing the resistance of yeast cells mainly due to a reduction of lipid oxidation. Especially for the iron compound, the data indicate complete protection when wild-type cells were exposed to H2O2 or O-2(center dot-) species. Interestingly, these compounds also compensate for both superoxide dismutase and catalase deficiencies; their antioxidant activity is metal ion dependent, in the order iron(III) > copper(II) > manganese(II). The protection mechanism employed by the complexes proved to be independent of the activation of transcription factors (such as Yap1, Hsf1, Msn2/Msn4) and protein synthesis. There is no direct relation between the in vitro and the in vivo antioxidant activities. (C) 2014 Elsevier Inc. All rights reserved.