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Strategies for improving the solubility and metabolic stability of griseofulvin analogues

  • Asger Bjørn Petersen
  • , G. Konotop
  • , N. H. M. Hanafiah
  • , Peter Hammershøj
  • , M. S. Raab
  • , A. Kraemer
  • , Mads Hartvig Clausen
  • German Cancer Research Center

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative effect in two cancer cell lines. We conclude that on balance, the formation of polar oximes is the most promising strategy for improving the properties of the analogues.
Original languageEnglish
JournalEuropean Journal of Medicinal Chemistry
Volume116
Pages (from-to)210-215
Number of pages6
ISSN0223-5234
DOIs
Publication statusPublished - 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Griseofulvin analogues
  • Anticancer
  • Synthesis
  • Antifungal
  • Metabolic stability

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