Unveiling the mechanism of activation of the Te(IV) prodrug AS101. New chemical insights towards a better understanding of its medicinal properties.

AS101 (Ammonium trichloro (dioxoethylene-O,O') tellurate) is an important hypervalent Te-based prodrug. Recently, we started a systematic investigation on AS101 with the aim to correlate its promising biological effects as a potent immunomodulator drug with multiple medicinal applications and its specific chemical properties. To date, a substantial agreement on the rapid conversion of the initial AS101 species into the corresponding TeOCl3- anion does exist, and this latter species is reputed as the pharmacologically active one. However, we realized that TeOCl3- could quickly undergo further steps of conversion in an aqueous medium, eventually producing the TeO2 species. Using a mixed experimental and theoretical investigation approach, we characterized the conversion process leading to TeO2 occurring both in pure water and in reference buffers at physiological-like pH. Our findings may offer a valuable "chemical tool" for a better description, interpretation -and optimization- of the mechanism of action of AS101 and Te-based compounds. This might be a starting point for improved AS101-based medicinal application. Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Lorenzo Chiaverini, Iogann Tolbatov, Alessandro Marrone, Tiziano Marzo, Tarita Biver, Diego La Mendola. Unveiling the mechanism of activation of the Te(IV) prodrug AS101. New chemical insights towards a better understanding of its medicinal properties. Journal of inorganic biochemistry. 2024 Jul;256:112567

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PMID: 38669911

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