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1.
Biochim Biophys Acta Mol Basis Dis ; 1868(10): 166475, 2022 10 01.
Article in English | MEDLINE | ID: mdl-35777688

ABSTRACT

The overproduction of reactive oxygen species (ROS) induces oxidative stress, a well-known process associated with aging and several human pathologies, such as cancer and neurodegenerative diseases. A large number of synthetic compounds have been described as antioxidant enzyme mimics, capable of eliminating ROS and/or reducing oxidative damage. In this study, we investigated the antioxidant activity of a water-soluble 1,10-phenantroline-octanediaoate Mn2+-complex on cells under oxidative stress, and assessed its capacity to attenuate alpha-synuclein (aSyn) toxicity and aggregation, a process associated with increased oxidative stress. This Mn2+-complex exhibited a significant antioxidant potential, reducing intracelular oxidation and increasing oxidative stress resistance in S. cerevisiae cells and in vivo, in G. mellonella, increasing the activity of the intracellular antioxidant enzymes superoxide dismutase and catalase. Strikingly, the Mn2+-complex reduced both aSyn oligomerization and aggregation in human cell cultures and, using NMR and DFT/molecular docking we confirmed its interaction with the C-terminal region of aSyn. In conclusion, the Mn2+-complex appears as an excellent lead for the design of new phenanthroline derivatives as alternative compounds for preventing oxidative damages and oxidative stress - related diseases.


Subject(s)
Antioxidants , Manganese , Phenanthrolines , alpha-Synuclein , Antioxidants/pharmacology , Manganese/pharmacology , Molecular Docking Simulation , Phenanthrolines/pharmacology , Reactive Oxygen Species , Saccharomyces cerevisiae , Water
2.
J Inorg Biochem ; 159: 120-32, 2016 06.
Article in English | MEDLINE | ID: mdl-26986979

ABSTRACT

The complexes [Ag2(OOC-(CH2)n-COO)] (n=1-10) (1-10) were synthesised and reacted with 1,10-phenanthroline (phen) to yield derivatives formulating as [Ag2(phen)x(OOC-(CH2)y-COO)]·zH2O (x=2 or 3; y=1-10; z=1-4) (11-20) which are highly water-soluble and photo-stable in aqueous solution. The phen derivatives 11-20 exhibit chemotherapeutic potential against Candida albicans, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and against cisplatin-sensitive breast (MCF-7) and resistant ovarian (SKOV-3) cancer cell lines. Cyclic voltammetric analysis and DNA binding and intercalation studies indicate that the mechanism of action of 11-20 is significantly different to that of their silver(I) dicarboxylate precursors and they do not induce DNA damage or ROS generation in mammalian cells. The representative complexes 9 and 19 (containing the undecanedioate ligand) were both found to significantly reduce superoxide and hydrogen peroxide induced oxidative stress in the yeast S. cerevisiae.


Subject(s)
Anti-Infective Agents , Antineoplastic Agents , Bacteria/growth & development , Breast Neoplasms/drug therapy , Candida albicans/growth & development , Ovarian Neoplasms/drug therapy , Phenanthrolines , Silver , Anti-Infective Agents/chemical synthesis , Anti-Infective Agents/chemistry , Anti-Infective Agents/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Intercalating Agents/chemical synthesis , Intercalating Agents/chemistry , Intercalating Agents/pharmacology , MCF-7 Cells , Ovarian Neoplasms/metabolism , Ovarian Neoplasms/pathology , Phenanthrolines/chemical synthesis , Phenanthrolines/chemistry , Phenanthrolines/pharmacology , Saccharomyces cerevisiae/metabolism , Silver/chemistry , Silver/pharmacology , Solubility
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