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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.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Xu Y,Wang Y,Zhao M,Hou B,Peng L,Zheng M,Wu J,Peng S

doi

10.1016/j.bmcl.2011.01.070

subject

Has Abstract

pub_date

2011-03-15 00:00:00

pages

1754-7

issue

6

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(11)00093-X

journal_volume

21

pub_type

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