Enzymatic oxidation of ansa-ferrocifen leads to strong and selective thioredoxin reductase inhibition in vitro
作者： Valeria Scalcon , Anna Citta , Alessandra Folda , Alberto Bindoli , Michèle Salmain
DOI: 10.1016/J.JINORGBIO.2016.08.005
关键词:
摘要: This paper reports the inhibitory effect on cytosolic thioredoxin reductase (TrxR1) in vitro by ansa-ferrocifen derivative (ansa-FcdiOH, 1). We found that 1 decreased only slightly enzyme activity (IC50 = 8 μM), while 1*, species generated enzymatic oxidation HRP (horseradish peroxidase)/H2O2 mixture, strongly inhibited TrxR1 0.15 μM). At same concentrations, neither nor 1* had glutathione (GR). The most potent inhibitor did not appear to be corresponding quinone methide as it was case for ferrocifens of acyclic series, or stabilized carbocation osmocifen but rather radical. hypothesis confirmed ab-initio calculations and EPR spectroscopy. BIAM (biotin-conjugated iodoacetamide) assay showed targeted both cysteine selenocysteine C-terminal redox center TrxR1.
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