Thioredoxin reductase: A target for gold compounds acting as potential anticancer drugs

摘要: The thioredoxin system plays a key role in regulating the overall intracellular redox balance. It basically comprises small protein (Trx), nicotinamide adenine dinucleotide phosphate, its reduced form (NADPH), and reductase (TrxR), large homodimeric selenzoenzyme controlling state of thioredoxin. Details are provided herein, particular emphasis being given to chemistry reductases. Several lines evidence point out today that represents an effective “druggable” target for development new anticancer agents. Accordingly, number established agents were retrospectively found be potent inhibitors reductases induce severe oxidative stress. During last decade variety gold compounds, either gold(I) or gold(III), reported manifest outstanding antitumor properties, forming promising class experimental In turn, recent studies have revealed several cytotoxic TrxR inhibitors. their mechanism selenoenzyme inhibition currently under investigation, our laboratory, some results will anticipated here; notably, preferential targeting active site selenolate could experimentally supported. Based on numerous evidences now available, both at molecular cellular level, we propose relevant actions produced by compounds mainly result reductase; alterations mitochondrial functions, elicited profound inhibition, would eventually lead cell apoptosis. A general unitary framework is thus offered interpret mode action according which they should primarily considered as antimitochondrial drugs. peculiar properties highlighted this review might further exploited obtainment newer selective