Halogenated Rocaglate Derivatives: Pan-antiviral Agents against Hepatitis E Virus and Emerging Viruses

  • J Med Chem. 2024 Jan 11;67(1):289-321. doi: 10.1021/acs.jmedchem.3c01357.
Catherine Victoria  1 ,  Göran Schulz  1 ,  Mara Klöhn  2 ,  Saskia Weber  3 ,  Cora M Holicki  3 ,  Yannick Brüggemann  2 ,  Miriam Becker  4 ,  Gisa Gerold  4  5  6 ,  Martin Eiden  3 ,  Martin H Groschup  3 ,  Eike Steinmann  2 ,  Andreas Kirschning  1
Affiliations
  • 1. Institute of Organic Chemistry, Leibniz University Hannover, Schneiderberg 1B, 30167 Hannover, Germany.
  • 2. Department of Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 3. Federal Research Institute in Animal Health (FLI), Südufer 10, 17493 Greifswald, Insel Riems, Germany.
  • 4. Institute for Biochemistry and Research Center for Emerging Infections and Zoonoses (RIZ), University of Veterinary Medicine Hannover, Bünteweg 2, 30559 Hannover, Germany.
  • 5. Wallenberg Centre for Molecular Medicine (WCMM), Umeå University, 901 87 Umeå, Sweden.
  • 6. Department of Clinical Microbiology, Virology, Umeå University, 901 87 Umeå, Sweden.
PMID: 38127656 DOI: 10.1021/acs.jmedchem.3c01357
Abstract

The synthesis of a library of halogenated rocaglate derivatives belonging to the flavagline class of natural products, of which silvestrol is the most prominent example, is reported. Their Antiviral activity and cytotoxicity profile against a wide range of pathogenic viruses, including hepatitis E, Chikungunya, Rift Valley Fever virus and SARS-CoV-2, were determined. The incorporation of halogen substituents at positions 4', 6 and 8 was shown to have a significant effect on the Antiviral activity of rocaglates, some of which even showed enhanced activity compared to CR-31-B and silvestrol.

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