Abstract
A series of organoselenium dihalides (organoselenanes) was synthesized from organoselenides using a chemoenzymatic approach. The organoselenanes have variations in their stereochemistry and in the halogen atom bonded to the selenium atom. Because of the unique selenium-thiol chemistry displayed by several organoselenium compounds, the organoselenanes were evaluated as new potential inhibitors of cysteine proteases (cathepsins S and V). By the analysis of the second-order rate constants of the inhibition of cathepsin S and V, it was possible to conclude that organoselenanes inhibited the cathepsin S faster than cathepsin V. It was observed higher inhibitory potencies for the dibromo organoselenanes derivatives than the dichloro analogues. In addition, the present data suggest the use of hypervalent selenium compounds as novel motifs for cysteine proteases inhibitors.
Highlights
The selenium compounds biological properties have been widely investigated,[1] especially because selenium is an essential trace element for mammals and organisms.[2]
Based on the structural catalytic proprieties of cysteine proteases and selenium(IV) chemistry, we report our investigation on the creation of a new class of selenium-containing compounds, organoselenanes (selenium(IV) compounds), to be used as novel inhibitors of human cysteine cathepsins S and V
We prepared a small series of seleniumcontaining compounds to be investigated as possible inhibitors of cysteine cathepsins, through which was possible to evaluate the influence of structural elements, such as the chirality and the effect of halogen derivatives (Figure 1)
Summary
The selenium compounds biological properties have been widely investigated,[1] especially because selenium is an essential trace element for mammals and organisms.[2]. Inspired by the sulfur reactivity with selenium compounds, we looked at the cysteine cathepsins, which are lysosomal cysteine proteases, and are often upregulated in various human cancers They have been implicated in distinct tumorigenic processes, such as angiogenesis, proliferation, and apoptosis and invasion.[15] The human family of cysteine cathepsins has 11 members (cysteine cathepsin B, C, F, H, K, L, O, S, V, W and X), which share a conserved active site that is formed by cysteine, histidine and asparagine residues.[16] Based on the structural catalytic proprieties of cysteine proteases and selenium(IV) chemistry, we report our investigation on the creation of a new class of selenium-containing compounds, organoselenanes (selenium(IV) compounds), to be used as novel inhibitors of human cysteine cathepsins S and V
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
