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A water-soluble manganese(II) octanediaoate/phenanthroline complex acts as an antioxidant and attenuates alpha-synuclein toxicity

Lookup NU author(s): Professor Tiago OuteiroORCiD

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Abstract

© 2022 Elsevier B.V. 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.

Publication metadata

Author(s): Queiroz DD, Ribeiro TDP, Goncalves JM, Mattos LMM, Gerhardt E, Freitas J, Palhano FL, Frases S, Pinheiro AS, McCann M, Knox A, Devereux M, Outeiro TF, Pereira MD

Publication type: Article

Publication status: Published

Journal: Biochimica et Biophysica Acta - Molecular Basis of Disease

Year: 2022

Volume: 1868

Issue: 10

Print publication date: 01/10/2022

Online publication date: 28/06/2022

Acceptance date: 23/06/2022

ISSN (print): 0925-4439

ISSN (electronic): 1879-260X

Publisher: Elsevier B.V.

URL: https://doi.org/10.1016/j.bbadis.2022.166475

DOI: 10.1016/j.bbadis.2022.166475

PubMed id: 35777688

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