title: Iron, copper, and manganese complexes with in vitro superoxide dismutase and/or catalase activities that keep Saccharomyces cerevisiae cells alive under severe oxidative stress.
abstract: 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 HPClNOL {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 (IC50~0.4 μmol 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 O2(•-) 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 O2(•-) 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.
authors.affiliation: Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-909, RJ, Brazil.
authors.forename: Thales P
authors.initials: TP
authors.lastname: Ribeiro
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fernandes
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil.
authors.forename: Karen V
authors.initials: KV
authors.lastname: Melo
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil.
authors.forename: Sarah S
authors.initials: SS
authors.lastname: Ferreira
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil.
authors.forename: Josane A
authors.initials: JA
authors.lastname: Lessa
authors.affiliation: Laboratório de Ciência Físicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil.
authors.forename: Roberto W A
authors.initials: RW
authors.lastname: Franco
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072, Australia.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Schenk
authors.affiliation: Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, 21941-909, RJ, Brazil. Electronic address: marcosdp@iq.ufrj.br.
authors.forename: Marcos D
authors.initials: MD
authors.lastname: Pereira
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro - Campos dos Goytacazes, 28013-602, RJ, Brazil. Electronic address: adolfo@uenf.br.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Horn
mesh_terms: D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology*; D055162:Biocatalysis; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000494:pharmacology*; D002374:Catalase / Q000737:chemistry / Q000378:metabolism; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D015870:Gene Expression; D006861:Hydrogen Peroxide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D007501:Iron / Q000737:chemistry*; D015227:Lipid Peroxidation / Q000187:drug effects; D008345:Manganese / Q000737:chemistry*; D050296:Microbial Viability / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D000975:Antioxidants; D056831:Coordination Complexes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013481:Superoxides; D008345:Manganese; D003300:Copper; D006861:Hydrogen Peroxide; D007501:Iron; D002374:Catalase; D013482:Superoxide Dismutase