Unveiling the mechanism of activation of the Te(IV) prodrug AS101. New chemical insights towards a better understanding of its medicinal properties.
J Inorg Biochem
; 256: 112567, 2024 07.
Article
en En
| MEDLINE
| ID: mdl-38669911
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Profármacos
Idioma:
En
Revista:
J Inorg Biochem
Año:
2024
Tipo del documento:
Article
País de afiliación:
Italia
Pais de publicación:
Estados Unidos