Flavipesines A and B and Asperchalasines E-H: Cytochalasans and Merocytochalasans from Aspergillus flavipes

J Nat Prod. 2019 Nov 22;82(11):2994-3001. doi: 10.1021/acs.jnatprod.9b00512. Epub 2019 Nov 1.

Abstract

Flavipesines A and B (1 and 2) and asperchalasines E-H (3-6), two cytochalasans with an unusual ring system and four merocytochalasans possessing a 5/6/11/5/5/6 ring system, were isolated from Aspergillus flavipes, along with three related compounds (7-9). Their structures, including absolute configurations, were determined on the basis of data from HRESIMS, NMR, ECD, molecular modeling, and single-crystal X-ray diffraction. Flavipesines A and B (1 and 2) represent the first examples of cytochalasans possessing a 5/6/7/6 ring system with a C-18-O-C-21 bridge. Compounds 3, 7, and 9 show moderate inhibitory activities against isocitrate dehydrogenase 1 (IDH1). This is the first report on the IDH1 inhibitory activities of cytochalasans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus / chemistry*
  • Computer Simulation
  • Cytochalasins / chemistry*
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Isocitrate Dehydrogenase / antagonists & inhibitors
  • Models, Molecular
  • Molecular Docking Simulation
  • Molecular Structure
  • X-Ray Diffraction

Substances

  • Cytochalasins
  • Enzyme Inhibitors
  • Isocitrate Dehydrogenase