New Cyclohexadepsipeptides from an Entomogenous Fungus Fusarium proliferatum and Their Cytotoxicity and Autophagy-Inducing Activity

Chem Biodivers. 2016 Jul;13(7):852-60. doi: 10.1002/cbdv.201500262. Epub 2016 Jun 16.

Abstract

Five new cyclohexadepsipeptides termed as enniatins R - V (1 - 5) and seven known cyclohexadepsipeptides (6 - 12) were isolated from the solid culture of Fusarium proliferatum, a fungus isolated from the cadaver of an unidentified insect collected in Tibet. Their structures were elucidated by NMR and MS spectroscopic analysis. The X-ray single-crystal structure of 6 was reported for the first time. Enniatins R and S represented the first enniatins incorporating with an unusual 2,3-dihydroxy-isovaleric acid (Div) residue. The cytotoxicity and autophagy-inducing activities of 1 - 12 were evaluated in vitro. Beauvenniatin F (11) exhibited strong cytotoxicity against K562/A (adriamycin-resistant K562) with IC50 value of 3.78 μm, and also autophagy-inducing activity at the concentration of 20 μm in GFP-LC3 stable HeLa cells.

Keywords: Autophagy-inducing activity; Cyclohexadepsipeptides; Cytotoxicity; Fusarium proliferatum.

MeSH terms

  • Antineoplastic Agents
  • Autophagy / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Crystallography, X-Ray
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification
  • Depsipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Fusarium / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Conformation
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Depsipeptides

Associated data

  • GENBANK/HF930594
  • GENBANK/KT207283