Lead Detoxification Activities of a Class of Novel DMSA鈥揂mino Acid Conjugates

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• 作者：Yanxia Xu ; Yuji Wang ; Ling Wang ; Ming Zhao ; Xiaoyi Zhang ; Xiaomin Hu ; Baoguang Hou ; Li Peng ; Meiqing Zheng ; Jianhui Wu ; Shiqi Peng
• 刊名：Chemical Research in Toxicology
• 出版年：2011
• 出版时间：June 20, 2011
• 年：2011
• 卷：24
• 期：6
• 页码：979-984
• 全文大小：722K
• 年卷期：v.24,no.6(June 20, 2011)
• ISSN：1520-5010

文摘

The coupling of the 1-carboxyl of DMSA with l-amino acids led to a class of novel 1-(carbonyl-l-amino-acid)-2,3-dimercaptosuccinic acids (DMSA鈥揳mino acid conjugates, DMSA-Gly, -Ser, -Val, -Leu, -Ile, -Asn, -Asp, -Gln, -Glu, -Met, -Phe, and -Trp). In the in vivo evaluation of Pb-loaded mice, 0.4 mmol/kg of the conjugates effectively decreased the Pb levels of the femur, brain, kidney, liver, and blood, greatly enhanced urination, and increased the Pb levels of both urine and feces, while causing no redistributions of Pb to the other organs, especially to the brain. With respect to lowering the bone and brain Pb, DMSA-Ile, -Asn, -Gln, and -Met were more effective than DMSA. This benefit was attributed to their high transmembrane ability. In contrast to Pb, the essential metals such as Fe, Cu, Zn, and Ca of the treated mice were not affected by the administration of the conjugates. Silico molecular modeling predicted that the conjugates had little hepatotoxicity, except possibly for DMSA-Phe.