Hypericins and Thioredoxin Reductase: Biochemical and Docking Studies disclose the Molecular Basis for Effective Inhibition by Naphthodianthrones

Cytosolic (TrxR1) and mitochondrial (TrxR2) thioredoxin reductases experience pronounced concentration- and time-dependent inhibition when incubated with the two naphthodianthrones hypericin and pseudohypericin. The important differences in the inhibitory potencies and profiles of the two compounds were analysed through a molecular modeling approach. The TrxR inhibition promoted by hypericin and pseudohypericin does not involve the active site selenol/thiol motif as confirmed by biochemical and modeling studies.