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

Exploring the antioxidant activity of Fe(III), Mn(III)Mn(II), and Cu(II) compounds in Saccharomyces cerevisiae and Galleria mellonella models of study

“…Using Galleria mellonella larvae we proved that the complexes act as antioxidants and are safe in terms of their toxicity. We have recently reported the use of G. mellonella larvae to investigate the antioxidant potential of a Mn 2+ -complex, [Mn 2 (μ 2 -oda)(phen) 4 (H 2 O) 2 ] 2+ , which reduced the susceptibility of this invertebrate model to H 2 O 2 stress (Queiroz et al 2022 ). Unquestionably, regardless of the treatment dose used, all complexes tested could prolong the survival of G. mellonella larvae.…”

“…Exponentially fermentative cells were directly exposed to oxidizing agents (1 mM H 2 O 2 or 30 mM menadione) and incubated at 28°C and 160 rpm for 1 h (Pereira et al 2003 , Castro et al 2007 ). To analyze the antioxidant activity of 1, 2 , and 3 , the cells were pretreated with increasing concentrations of the complexes for 1 h at 28°C and 160 rpm (Ribeiro et al 2015 , Queiroz et al 2022 ). Next, the cells were harvested, washed twice with sterile water, resuspended in the original culture medium, previously centrifuged, and then subjected to oxidative stress.…”

“…To analyze the susceptibility of G. mellonella under oxidative stress conditions, larvae from the 7 th instars were subjected to H 2 O 2 (5 M) stress, which was directly injected (10 µl) in the last left pro-leg, using a Hamilton syringe, into the hemocoel of G. mellonella larvae (Queiroz et al 2022 ). A group of G. mellonella larvae, previously treated with 1, 2, or 3 at different dosages (50 mg.kg −1 , 125 mg.kg −1 , and 250 mg.kg −1 ), was also stressed with 5 M H 2 O 2 .…”

“…Interestingly, the efficacy of these complexes appears to be related to the reduction of protein and lipid oxidation, as well as the modulation of metal homeostasis in the intracellular milieu (Ribeiro et al 2015 , 2017 ). More recently, a 1,10-phenantroline-octanediaoate Mn 2+ -complex was reported exhibiting significant antioxidant potential, modulating intracellular oxidation and decreasing the susceptibility of S. cerevisiae cells and G. mellonella larvae to oxidative stress (Queiroz et al 2022 ). Moreover, this Mn 2+ -complex also attenuated the toxicity and aggregation of alpha-synuclein (αSyn), a human protein related to Parkinson´s disease, by interacting with negatively charged acidic residues (e.g.…”

“…Moreover, this Mn 2+ -complex also attenuated the toxicity and aggregation of alpha-synuclein (αSyn), a human protein related to Parkinson´s disease, by interacting with negatively charged acidic residues (e.g. Asp135) located at the C-terminal region of αSyn monomers (Queiroz et al 2022 ). Altogether, it is somewhat evident that synthetic antioxidants become an interesting alternative for therapeutic use against oxidative stress-related pathologies.…”