Lead detoxification activity and ADMET hepatotoxicity of N-(alpha-L-arabino-furanos-1-yl)-L-cysteine.
N-(alpha-L-Arabinofuranos-1-yl)-L-cysteine was stereoselectively prepared from L-arabinose and l-cysteine. Its in vivo detoxification action was evaluated on lead loaded mice at the doses of 0.1, 0.2, and 0.4 mmol/kg. The results show that lead accumulation in the livers, kidneys, brains, and femurs of the treated mice could be efficiently decreased by N-(alpha-L-arabinofuranos-1-yl)-L-cysteine, even at the dose of 0.1 mmol/kg. Compared with the lead detoxification efficacy, 0.4 mmol/kg of N-(alpha-L-arabinofuranos-1-yl)-L-cysteine did not affect the essential metals in the treated mice, such as Fe, Cu, Zn, and Ca. In the apparent permeability coefficient test, the values of P(app)(A-->B), P(app)(B-->A), and P(app)(A-->B)/P(app)(B-->A) indicated that N-(alpha-L-arabinofuranos-1-yl)-L-cysteine was transported actively across the Caco-2 cell monolayer. Silico molecular modeling results predicted that N-(alpha-L-arabinofuranos-1-yl)-L-cysteine had no hepatotoxicity.
Zhao
Ming
M
College of Pharmaceutical Sciences, Capital Medical University, Beijing, PR China.
Wang
Yuji
Y
Huo
Caixia
C
Liu
Jiawang
J
Li
Chunyu
C
Zhang
Xiaoyi
X
Peng
Li
L
Peng
Shiqi
S
D000818:Animals; D001089:Arabinose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D006801:Humans; D007854:Lead / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D008297:Male; D051379:Mice; D013237:Stereoisomerism
C553656:N-(arabinofuranos-1-yl)cysteine; D007854:Lead; D001089:Arabinose; D003545:Cysteine