University of Hertfordshire

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  • 906925

    Final published version, 1.59 MB, PDF document

  • Tummala Rama Krishna Reddy
  • Chan Li
  • Xiaoxia Guo
  • Peter Fischer
  • Lodewijk Dekker
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Original languageEnglish
Pages (from-to)5378-5391
JournalBioorganic and Medicinal Chemistry
Volume22
Issue19
DOIs
Publication statusPublished - 1 Oct 2014

Abstract

Recent target validation studies have shown that inhibition of the protein interaction between annexin A2 and the S100A10 protein may have potential therapeutic benefits in cancer. Virtual screening identified certain 3,4,5-trisubstituted 4H-1,2,4-triazoles as moderately potent inhibitors of this interaction. A series of analogues were synthesized based on the 1,2,4-triazole scaffold and were evaluated for inhibition of the annexin A2–S100A10 protein interaction in competitive binding assays. 2-[(5-{[(4,6-Dimethylpyrimidin-2-yl)sulfanyl]methyl}-4-(furan-2-ylmethyl)-4H-1,2,4-triazol-3-yl)sulfanyl]-N-[4-(propan-2-yl)phenyl]acetamide (36) showed improved potency and was shown to disrupt the native complex between annexin A2 and S100A10

Notes

The work described here was supported by Cancer Research UK (Grant reference C21559/A11597 and C21559/A7252). Copyright 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).

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