2014年8月
In silico and pharmacological screenings identify novel serine racemase inhibitors
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
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- 巻
- 24
- 号
- 16
- 開始ページ
- 3732
- 終了ページ
- 3735
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1016/j.bmcl.2014.07.003
- 出版者・発行元
- PERGAMON-ELSEVIER SCIENCE LTD
D-Serine is a coagonist of the N-methyl-D-aspartate (NMDA)-type glutamate receptor and its biosynthesis is catalyzed by serine racemase (SR). The overactivation of the NMDA receptor has been implicated in the development of neurodegenerative diseases, strokes, and epileptic seizures, thus, the inhibitors of SR have potential against these pathological states. Here, we have developed novel inhibitors of SR by in silico screening and in vitro enzyme assay. The newly developed inhibitors have lower IC50 value comparing with that of malonate, one of the standard SR inhibitor. The structural features of novel inhibitors suggest the importance of central amide structure having a phenoxy substituent in their structure for the SR inhibitory activity. The present findings suggest the importance and rational development of new drugs for diseases of NMDAR overactivation. (C) 2014 Elsevier Ltd. All rights reserved.
- リンク情報
- ID情報
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- DOI : 10.1016/j.bmcl.2014.07.003
- ISSN : 0960-894X
- eISSN : 1464-3405
- PubMed ID : 25066953
- Web of Science ID : WOS:000340565900011