The Anticancer Activity of Organotelluranes: Potential Role in Integrin Inactivation

Abstract

Organic Te(IV) compounds (organotelluranes) differing in their labile ligands exhibited anti-integrin activities in vitro and anti-metastatic properties in vivo. They underwent ligand substitution with l-cysteine, as a thiol model compound. Unlike inorganic Te(IV) compounds, the organotelluranes did not form a stable complex with cysteine, but rather immediately oxidized it. The organotelluranes inhibited integrin functions, such as adhesion, migration, and metalloproteinase secretion mediation in B16F10 murine melanoma cells. In comparison, a reduced derivative with no labile ligand inhibited adhesion of B16F10 cells to a significantly lower extent, thus pointing to the importance of the labile ligands of the Te(IV) atom. One of the organotelluranes inhibited circulating cancer cells in vivo, possibly by integrin inhibition. Our results extend the current knowledge on the reactivity and mechanism of organotelluranes with different labile ligands and highlight their clinical potential.

Crystallographic and docking (Cathepsins B, K, L and S) studies on bioactive halotelluroxetanes

“…Research on this non-toxic compound shows the cation to be a specific covalent inhibitor of cysteine proteases such as papain and Cathepsin B [26]. These observations have encouraged further studies of tellurium- 3 (22) based compounds as inhibitors of this class of enzyme.…”

“…The most notable tellurium compound that exerts biological activity is found in the salt ammonium trichlorido (dioxyethylene-O,Oꞌ)tellurate, known as AS-101 ( Figure 1a) [25]. This low-molecular weight organotellurate is a potent immunomodulator [26] that has been in clinical trials for psoriasis [27], topical treatment for human papillomavirus [28], prevention of infertility in chemotherapy patients [29] and for inhibition of angiogenesis [24,30].…”

Crystal structure of (E)-dichloro(1-chloro-3-methoxyprop-1-en-2-yl)(4-methoxyphenyl)-λ4-tellane, C11H13Cl3O2Te

“…While not as well recognised as selenium compounds, tellurium species are known to exhibit exciting biological responses [7,8]. Experiments [9], confirmed by molecular docking studies [10], indicate that cysteine proteases, such as Cathepsin B, are key targets for thiophilic tellurium compounds, owing to the presence of a cysteine residue in the active site. This is important as the inhibition of Cathepsin B results in the disruption of crucial cellular processes.…”

Expanding beyond canonical metabolism: Interfacing alternative elements, synthetic biology, and metabolic engineering

“…These molecules include dimethyl telluride, dimethyl ditelluride, methanetellurol, and dimethyl tellurenyl sulfide, but have yet to be found useful for downstream applications. Much like selenium, certain tellurium compounds possess chemopreventative, anticancer, and antibiotic properties but extensive research is needed due to the toxicity of tellurium compounds, especially relative to human health [122] , [123] .…”