Antioxidant activity and cellular uptake of the hydroxamate-based fungal iron chelators pyridoxatin, desferriastechrome and desferricoprogen

Author(s)

da Silva, Gabriel Souto ^[1] ; Shang, Zhuo ^[2] ; Kalansuriya, Pabasara ^[2] ; Capon, Robert J. ^[2] ; Esposito, Breno Pannia ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Chem, Dept Fundamental Chem, BR-05508000 Sao Paulo - Brazil

^[2] Univ Queensland, Inst Mol Biosci, Brisbane, Qld - Australia

• Document type: Journal article
• Source: BIOMETALS; v. 32, n. 4, p. 707-715, AUG 2019.
• Web of Science Citations: 0

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. (AU)

• FAPESP's process: 16/03709-9 - Modulation of the levels and reactivity of physiological iron by mean of new natural or bifunctional chelators: possible applications in human health
• Grantee: Breno Pannia Esposito
• Support Opportunities: Regular Research Grants