title: Lead detoxification activities and ADMET hepatotoxicities of a class of novel 5-(1-carbonyl-L-amino-acid)-2,2-dimethyl-[1,3]dithiolane-4-carboxylic acids.
abstract: By linking the mercapto groups with isopropyl and introducing L-amino acid into the 5-carboxyl of DMSA a class of novel 5-(1-carbonyl-L-amino-acid)-2,2- dimethyl-[1,3]dithiolane-4-carboxylic acids were prepared. Their in vivo activities were evaluated on lead loaded mice at the dose of 0.4 mmol/kg. The results showed that the lead levels of the livers, kidneys, femurs and brains in particular could be efficiently decreased by 0.4 mmol/kg of 5-(1-carbonyl-L-amino-acid)-2,2-dimethyl-[1,3]dithiolane-4-carboxylic acids. The benefit of 5-(1-carbonyl-L-amino-acid)-2,2-dimethyl-[1,3]dithiolane-4-carboxylic acids to the detoxification of the brain lead was attributed to their transmembrane ability. Compared with the lead detoxification efficacy, they did not affect the essential metals such as Fe, Cu, Zn, and Ca of the treated mice. Silico molecular modeling predicted that 5-(1-carbonyl-L-amino-acid)-2,2-dimethyl-[1,3]dithiolane-4-carboxylic acids had no hepatotoxicity.
authors.affiliation: College of Pharmaceutical Sciences, Peking University, Beijing, PR China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Xu
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Baoguang
authors.initials: B
authors.lastname: Hou
authors.forename: Li
authors.initials: L
authors.lastname: Peng
authors.forename: Meiqing
authors.initials: M
authors.lastname: Zheng
authors.forename: Jianhui
authors.initials: J
authors.lastname: Wu
authors.forename: Shiqi
authors.initials: S
authors.lastname: Peng
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000633:toxicity*; D007854:Lead / Q000633:toxicity*; D008107:Liver Diseases / Q000209:etiology*; D051379:Mice
chemical_list: D002264:Carboxylic Acids; D007854:Lead