Abstract
The hydroxamate class of compounds is well known for its pharmacological applications, especially in the context of chelation therapy. In this work we investigate the performance of the fungal hydroxamates pyridoxatin (PYR), desferriastechrome (DAC) and desferricoprogen (DCO) as mitigators of stress caused by iron overload (IO) both in buffered medium and in cells. Desferrioxamine (DFO), the gold standard for IO treatment, was used as comparison. It was observed that all the fungal chelators (in aqueous medium) or PYR and DAC (in cells) are powerful iron scavengers. However only PYR and DCO (in aqueous medium) or PYR (in cells) were also antioxidant against two forms of iron-dependent oxidative stress (ascorbate or peroxide oxidation). These findings reveal that PYR is an interesting alternative to DFO for iron chelation therapy, since it has the advantage of being cell permeable and thus potentially orally active.
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Acknowledgements
G.S.S. was the Recipient of a MSc Grant from National Council for Scientific and Technological Development (CNPq-Brazil). B.P.E. was funded by São Paulo Science Foundation (FAPESP; 2016/03709-9 and 2013/13166-4). The authors thank the assistance of Mrs Jéssica B. N. Esposito in the experiments with cells.
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da Silva, G.S., Shang, Z., Kalansuriya, P. et al. Antioxidant activity and cellular uptake of the hydroxamate-based fungal iron chelators pyridoxatin, desferriastechrome and desferricoprogen. Biometals 32, 707–715 (2019). https://doi.org/10.1007/s10534-019-00202-7
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DOI: https://doi.org/10.1007/s10534-019-00202-7