Wortmannilactones I-L, new NADH-fumarate reductase inhibitors, induced by adding suberoylanilide hydroxamic acid to the culture medium of Talaromyces wortmannii

Bioorg Med Chem Lett. 2016 Nov 1;26(21):5328-5333. doi: 10.1016/j.bmcl.2016.09.032. Epub 2016 Sep 14.

Abstract

With the aim of finding more potential inhibitors against NADH-fumarate reductase (specific target for treating helminthiasis and cancer) from natural resources, Talaromyces wortmannii was treated with the epigenome regulatory agent suberoylanilide hydroxamic acid, which resulted in the isolation of four new wortmannilactones derivatives (wortmannilactones I-L, 1-4). The structures of these new compounds were elucidated based on IR, HRESIMS and NMR spectroscopic data analyses. These four new compounds showed potent inhibitory activity against NADH-fumarate reductase with the IC50 values ranging from 0.84 to 1.35μM.

Keywords: Epigenome manipulation; NADH-fumarate reductase; Suberoylanilide hydroxamic acid; Talaromyces wortmannii; Wortmannilactones.

MeSH terms

  • Culture Media
  • Hydroxamic Acids / pharmacology*
  • Macrolides / chemistry
  • Macrolides / pharmacology*
  • Molecular Structure
  • Oxidoreductases Acting on CH-CH Group Donors / antagonists & inhibitors*
  • Spectrum Analysis / methods
  • Talaromyces / chemistry*
  • Vorinostat

Substances

  • Culture Media
  • Hydroxamic Acids
  • Macrolides
  • Vorinostat
  • Oxidoreductases Acting on CH-CH Group Donors
  • fumarate reductase (NADH)