Structure-Based Reactivity Profiles of Reactive Metabolites with Glutathione.
Chem Res Toxicol
; 33(7): 1579-1593, 2020 07 20.
Article
em En
| MEDLINE
| ID: mdl-32347096
ABSTRACT
Therapeutic agents can be transformed into reactive metabolites under the action of various metabolic enzymes in vivo and then covalently combine with biological macromolecules (such as protein or DNA), resulting in increasing toxicity. The screening of reactive metabolites in drug discovery and development stages and monitoring of biotransformation in post-market drugs has become an important research field. Generally, reactive metabolites are electrophilic and can be captured by small nucleophiles. Glutathione (GSH) is a small peptide composed of three amino acids (i.e., glutamic acid, cysteine, and glycine). It has a thiol group which can react with electrophilic groups of reactive metabolic intermediates (such as benzoquinone, N-acetyl-p-benzoquinoneimine, and Michael acceptor) to form a stable binding conjugate. This paper aims to provide a review on structure-based reactivity profiles of reactive metabolites with GSH. Furthermore, this review also reveals the relationship between drugs' molecular structures and reactive metabolic toxicity from the perspective of metabolism, giving a reference for drug design and development.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Orgânicos
/
Glutationa
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Chem Res Toxicol
Assunto da revista:
TOXICOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
China