期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 24, 期 1, 页码 386-389出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2013.10.068
关键词
Captopril; NDM-1 inhibitor; Metalantidote; 3-Mercapto-2-methylpropanoic acid
资金
- National Natural Science Foundation of China (NSFC) [21072106, 21372129, 81102374]
- National Biomedical Special Project of International Innovation Park [11ZCKFSY06800]
- Fok Ying Tong Education Foundation [122037]
- Program for New Century Excellent Talents in University
- Scientific Research Starting Foundation of Returned Overseas Chinese Scholars, Ministry of Education of China
- '111' Project of the Ministry of Education of China [B06005]
- National Program on Key Basic Research [2013CB967200]
Captopril is a New Delhi metallo-beta-lactamase-1 (NDM-1) inhibitor with an IC50 value of 7.9 mu M. It is composed of two units: a 3-mercapto-2-methylpropanoyl fragment and a proline residue. In this study, we synthesized simple amide derivatives of 3-mercapto-2-methylpropanoic acid, and then tested them as NDM-1 inhibitors in order to identify the pharmacophore for NDM-1 inhibition. We found that the lead compound 22 had an IC50 value of 1.0 mu M. Further structure simplification provided compounds 31 and 32, which had IC50 values of 15 and 10 mu M, respectively. As compound 32 is a clinically used antidote for metal poisoning, it has great potential to be repurposed to treat bacterial infections. (c) 2013 Elsevier Ltd. All rights reserved.
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