Azaphilone Derivatives from the Fungus Coniella fragariae Inhibit NF-κB Activation and Reduce Tumor Cell Migration

J Nat Prod. 2018 Nov 26;81(11):2493-2500. doi: 10.1021/acs.jnatprod.8b00540. Epub 2018 Oct 24.

Abstract

Seven new azaphilones, coniellins A-G (1-7), were obtained from the fungus Coniella fragariae that had been isolated from goose dung. Their structures were elucidated by analysis of 1D and 2D NMR as well as HRESIMS data. TDDFT-ECD calculation was used to determine the absolute configuration of 1, while Mosher's method was applied to determine the absolute configuration of 5. While displaying only moderate cytotoxicity, compound 1 exhibited significant inhibition of NF-κB activation in the triple negative breast cancer cell line MDA-MB-231 with an IC50 value of 4.4 μM. Moreover, compounds 1, 4, and 5 clearly reduced tumor cell migration. Compound 1 was the most active derivative tested in this assay and displayed 60% inhibition of tumor cell migration at a dose of 5 μM and 98% inhibition at 10 μM after 24 h.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Ascomycota / chemistry*
  • Benzopyrans / chemistry*
  • Benzopyrans / isolation & purification
  • Benzopyrans / pharmacology
  • Cell Line, Tumor
  • Cell Migration Inhibition
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Drug Screening Assays, Antitumor
  • Humans
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • NF-kappa B / antagonists & inhibitors*
  • Pigments, Biological / chemistry*
  • Pigments, Biological / isolation & purification
  • Pigments, Biological / pharmacology

Substances

  • Antineoplastic Agents
  • Benzopyrans
  • NF-kappa B
  • Pigments, Biological
  • azaphilone