Back to Search Start Over

Medicinal Hypervalent Tellurium Prodrugs Bearing Different Ligands: A Comparative Study of the Chemical Profiles of AS101 and Its Halido Replaced Analogues

Authors :
Lorenzo Chiaverini
Damiano Cirri
Iogann Tolbatov
Francesca Corsi
Ilaria Piano
Alessandro Marrone
Alessandro Pratesi
Tiziano Marzo
Diego La Mendola
Source :
International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7505
Publication Year :
2022

Abstract

Ammonium trichloro (dioxoethylene-O,O′) tellurate (AS101) is a potent immunomodulator prodrug that, in recent years, entered various clinical trials and was tested for a variety of potential therapeutic applications. It has been demonstrated that AS101 quickly activates in aqueous milieu, producing TeOCl3−, which likely represents the pharmacologically active species. Here we report on the study of the activation process of AS101 and of two its analogues. After the synthesis and characterization of AS101 and its derivatives, we have carried out a comparative study through a combined experimental and computational analysis. Based on the obtained results, we describe here, for the first time, the detailed reaction that AS101 and its bromido- and iodido-replaced analogues undergo in presence of water, allowing the conversion of the original molecule to the likely true pharmacophore. Interestingly, moving down in the halogens’ group we observed a higher tendency to react, attributable to the ligands’ effect. The chemical and mechanistic implications of these meaningful differences are discussed.

Details

Language :
English
Database :
OpenAIRE
Journal :
International Journal of Molecular Sciences; Volume 23; Issue 14; Pages: 7505
Accession number :
edsair.doi.dedup.....7fe4a48bcd37385585948ce239e66340