期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 22, 期 5, 页码 2084-2088出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.01.011
关键词
Periodontitis; Gram-negative anaerobe; Haloacid dehalogenase; HTS; Competitive inhibitor; Malachite green colorimetric method
资金
- National Research Foundation of Korea Government [2011-0030027]
- World Class Institute of the National Research Foundation of Korea
- Ministry of Education, Science and Technology
- National Research Foundation of Korea [2011-0030027] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
The serine phosphatase SerB653 plays a crucial role in the infection of Porphyromonas gingivalis, which contributes to the pathogenesis of periodontitis, an inflammatory disease of teeth-supporting tissues. Because functional loss of SerB653 eliminates the virulence of P. gingivalis, SerB653 inhibitors are considered potential periodontitis therapeutic or preventive agents. To identify SerB653 inhibitors with potent anti-periodontitis activity, we conducted a high-throughput screen of a representative 6800-compound subset of a synthetic chemical library of the Korea Chemical Bank (KCB) for compounds with activity against SerB653. The primary screening yielded 150 hits, and subsequent confirmatory studies identified eight compounds, mainly within a single cluster of 3-acyl-2-phenylamino-1,4-dihydroquinolin-4-one derivatives, that showed greater than 50% inhibition of SerB653 activity at a concentration of 50 mu M. A second screening with a focused library identified 10 compounds with IC50 values less than 10 mu M. In antibacterial tests, three of these compounds showed a minimum inhibitory concentration against P. gingivalis growth of 5-50 nM. (C) 2012 Elsevier Ltd. All rights reserved.
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