title: Antioxidant effect of 1,3,4-thiadiazolium mesoionic derivatives on isolated mitochondria.
abstract: Mesoionic compounds have shown antitumor and citotoxic activity against different tumor cells lines, which has been attributed to their physical and chemical characteristics. Among these compounds, the 1,3,4-thiadiazolium-2-phenylamine derivatives have been highlighted due to their important anti-melanoma activity. In this work, the effects of three derivatives that belong this class, MI-J, MI-4F and MI-2,4diF, on the oxidative stress parameters were evaluated using rat liver mitochondria. All the derivatives prevented natural and calcium induced oxidation of pyridine nucleotides at lower concentrations (6.5 and 32.5nmol/mg protein). The calcium uptake was inhibited by all the derivatives at higher concentrations (65 and 130nmol/mg protein), whereas the cation efflux was inhibited only by the MI-J (52%) and MI-4F (50%), possibly by inhibiting the formation of the permeability transition pore (PTP) by 100% and 50%, respectively, as observed in the same experimental conditions. MI-2,4diF did not inhibit the mitochondrial permeability transition or calcium efflux. The enzymatic activity of glutathione reductase, glutathione peroxidase and catalase was not affected by any derivative, but superoxide dismutase was inhibited by all the derivatives. MI-J inhibited enzyme activity significantly (85%) at the highest concentration (130nmol/mg protein); on the other hand, their activity was less affected by fluorine derivatives (MI-4F-20% and MI-2,4diF-32%). These results suggest that these derivatives exert antioxidant effects on isolated mitochondria.
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Amanda do Rocio
authors.initials: Ado R
authors.lastname: Andrade Pires
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Jabor Gozzi
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Guilhermina
authors.initials: G
authors.lastname: Rodrigues Noleto
authors.affiliation: Department of Chemistry, Federal Rural University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Aurea
authors.initials: A
authors.lastname: Echevarria
authors.affiliation: Department of Chemistry, Federal Rural University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Camilla
authors.initials: C
authors.lastname: Moretto Reis
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Maria Eliane
authors.initials: ME
authors.lastname: Merlin Rocha
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil.
authors.forename: Glaucia
authors.initials: G
authors.lastname: Regina Martinez
authors.affiliation: Department of Biochemistry and Molecular Biology, Federal University of Paraná, Curitiba, PR, Brazil. Electronic address: silvia.cadena@ufpr.br.
authors.forename: Silvia Maria Suter
authors.initials: SM
authors.lastname: Correia Cadena
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D009711:Nucleotides / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D009711:Nucleotides; D013830:Thiadiazoles; D002118:Calcium
keywords: 1,3,4-Thiadiazolium mesoionic derivatives; Liver mitochondria; Oxidative stress