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Reactive oxygen species (ROS) are closely related to oxidative stress, aging, and the onset of human diseases. To mitigate ROS-induced damages, extensive research has focused on examining the antioxidative attributes of various synthetic/natural substances. Coordination compounds serving as synthetic antioxidants have emerged as a promising approach to attenuate ROS toxicity. Herein, we investigated the antioxidant potential of a series of Fe(III) (1), Mn(III)Mn(II) (2) and Cu(II) (3) coordination compounds synthesized with the ligand N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]-propylamine in Saccharomyces cerevisiae exposed to oxidative stress. We also assessed the antioxidant potential of these complexes in the alternative model of study, Galleria mellonella. DPPH analysis indicated that these complexes presented moderate antioxidant activity. However, treating Saccharomyces cerevisiae with 1, 2 and 3 increased the tolerance against oxidative stress and extended yeast lifespan. The treatment of yeast cells with these complexes decreased lipid peroxidation and catalase activity in stressed cells, whilst no change in SOD activity was observed. Moreover, these complexes induced the Hsp104 expression. In G. mellonella, complex administration extended larval survival under H2O2 stress and did not affect the insect's life cycle. Our results suggest that the antioxidant potential exhibited by these complexes could be further explored to mitigate various oxidative stress-related disorders., (© The Author(s) 2023. Published by Oxford University Press on behalf of FEMS.)

Antioxidant activity toward H 2 O 2 , anion radical superoxide, hydroxyl and DPPH (2,2-diphenyl-1-picrylhydrazyl) of two manganese complexes [Mn(III)(bpa) 2 ]Cl.H 2 O (1) and [(Cl)Mn(μ-hbpclnol)(μ-bpclnol)Mn](ClO 4 ).3H 2 O (2) (hbpa = (2-hydroxybenzyl-2-pyridylmethyl)amine and h 2 bpclnol = (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine) are presented. X-ray diffraction studies were performed for complex (1). Both complexes presented similar or better activities than reference complex [Mn(salen)Cl], when the interaction between them and ROS (H 2 O 2 , O 2 •- and • OH), was monitored, by EPR (Electron Paramagnetic Resonance), in PBS, DMSO and water. The antioxidant activity rank of complexes toward • OH, generated by Fenton reaction and monitored by EPR, is (2) > (1) > [Mn(salen)Cl], in water (0.1% of DMSO for each complex), with the values of the IC 50 of 7.2 (±1.6), 15.5 (±1.8) and 29.1 (±2.01) μM respectively. EPR data presented herein suggest that complex (2) presents the better scavenging activity toward hydroxyl, being in good agreement with TBARS assay results, in which complex (2) presented the best inhibitory activity toward lipid peroxidation, employing Swiss mice liver homogenate tissue model. IC 50 values obtained from the interaction between these complexes and hydroxyl, using TBARS method, were: 0.88 (± 0.029); 0.73 (± 0.01) and 42.7 (± 3.5) nM, respectively for (1), (2) and [Mn(salen)Cl]. Complexes (1) and (2) are regulating the lipid homeostasis, protecting the tissue from the lipid peroxidation, in nanomolar scale, motivating in vivo studies. Redox properties and radical scavenging activity of complexes toward DPPH are non-linear and solvent dependent. Furthermore, the monitoring of antioxidant activity probed by EPR could be a fair and appropriate study to guide more advanced investigations., Competing Interests: Declaration of Competing Interest The authors declare that they have no any conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The interaction between Cu II , Fe III and Mn II complexes, derived from the ligands 1-[bis(pyridine-2-ylmethyl)amino]-3-chloropropan-2-ol (hpclnol) and bis(pyridine-2-ylmethyl)amine (bpma), and the free radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl)hydrazyl (DPPH) and reactive oxygen species (ROS), was investigated by colorimetric and EPR (Electron Paramagnetic Resonance) techniques. A comparison between these results and those reported to [Mn(salen)Cl] or EUK-8 was also addressed. EPR studies allowed us the identification of intermediates species such as superoxide‑copper(I) and superoxide‑copper(II), a mixed-valence Fe III Fe II species and a 16-line feature attributed to Mn III -oxo-Mn IV species. The biomarker malondialdehyde (MDA) was determined by TBARS assay in S. cerevisiae cells, and the determination of the IC 50 indicate that the antioxidant activity shown dependence on the metal center (Cu II  ≈ Fe III  > Mn II  ≈ [Mn(salen)Cl]. The lipid peroxidation attenuation was also investigated in liver homogenates obtained from Swiss mice and the IC 50 values were in the nanomolar concentrations. We demonstrated here that all the complexes interact with the free radical DPPH and with ROS (H 2 O 2 , O 2 •- and hydroxyl radical), enhancing the cellular protection against oxidative stress generated by hydroxyl radical, employing two experimental model systems, S. cerevisiae (in vivo) and mouse liver (ex vivo)., Competing Interests: Declaration of Competing Interest The authors declare that they have no any conflict of interest., (Copyright © 2022. Published by Elsevier Inc.)

Chagas disease is a neglected tropical disease caused by the protozoan pathogen Trypanosoma cruzi . The disease is a major public health problem affecting about 6 to 7 million people worldwide, mostly in Latin America. The available therapy for this disease is based on two drugs, nifurtimox and benznidazole, which exhibit severe side effects, including resistance, severe cytotoxicity, variable efficacy and inefficiency in the chronic phase. Therefore, new drugs are urgently needed. Coordination compounds may be an interesting alternative for antiparasite therapy against Leishmania spp., Toxoplasma gondii and T. cruzi . Herein, we tested the in vitro effect on T. cruzi epimastigotes (Y strain) of two new μ-oxo Fe(III) dinuclear complexes: [(HL1)(Cl)Fe(μ-O)Fe(Cl)(HL2)](Cl) 2 ·(CH 3 CH 2 OH) 2 ·H 2 O (1) and [(HL2)(Cl)Fe(μ-O)Fe(Cl)(HL2)](Cl) 2 ·H 2 O (2) where HL1 and HL2 are ligands which contain two pyridines, amine and alcohol moieties with a naphthyl pendant unit yielding a N 3 O coordination environment. Complexes (1) and (2), which are isomers, were completely characterized, including X-ray diffraction studies for complex (1). Parasites were treated with the complexes and the outcome was analyzed. Complex (1) exhibited the lowest IC 50 values, which were 99 ± 3, 97 ± 2 and 110 ± 39 nM, after 48, 72 and 120 h of treatment, respectively. Complex (2) showed IC 50 values of 118 ± 5, 122 ± 6 and 104 ± 29 nM for the same treatment times. Low cytotoxicity to the host cell LLC-MK2 was found for both complexes, resulting in impressive selectivity indexes of 106 for complex (1) and 178 for (2), after 120 h of treatment. Treatment with both complexes reduced the mitochondrial membrane potential of the parasite. Ultrastructural analysis of the parasite after treatment with complexes showed that the mitochondria outer membrane presented swelling and abnormal disposition around the kinetoplast; in addition, reservosomes presented anomalous spicules and rupture. The complexes showed low nanomolar IC 50 values affecting mitochondria and reservosomes, essential organelles for the survival of the parasite. The low IC 50 and the high selectivity index show that both complexes act as a new prototype of drugs against T. cruzi and may be used for further development in drug discovery to treat Chagas disease.