Selenocysteine of thioredoxin reductase as the primary target for the antitumor metallodrugs: A computational point of view

Selenocysteine (Sec) has been recognized as a soft metal-coordinating residue that dues its relevance to the important role played in the catalytic activity of thioredoxin reductase (TrxR), a well-characterized an-ticancer target. Thus, several computational studies have been devoted to the metalation of this Se-based residue and several metal scaffolds have been proposed as potential Sec-binders, i.e. TrxR inhibitors. Here, we reported an overview of the chemical features of Sec, as well as of typical Sec-binding metal com-plexes, and of the computational studies carried on metallodrugs that primary target TrxR, by specifically posing our attention to antitumour metallodrugs based on Au(I), Au(III), Ag(I), Pt(II), Pt(IV), Ru(II), Ru(III), and Rh(III) metal centers. Moreover, we provided a computational insight on the available structural data and highlighted how an optimal articulation of computational methods and modeling of the metallodrug-target system may expand our understanding of the targeting of TrxR active site by metallic scaffolds.(c) 2022 Elsevier B.V. All rights reserved.