Geospallins A⁻C: New Thiodiketopiperazines with Inhibitory Activity against Angiotensin-Converting Enzyme from a Deep-Sea-Derived Fungus Geosmithia pallida FS140

Mar Drugs. 2018 Nov 23;16(12):464. doi: 10.3390/md16120464.

Abstract

Three new thiodiketopiperazines, geospallins A⁻C (1⁻3), together with nine known analogues (4⁻12), were isolated from the culture of the deep-sea sediment-derived fungus Geosmithia pallida FS140. Among them, geospallins A and B (1 and 2) represent rare examples of thiodiketopiperazines featuring an S-methyl group at C-10 and a tertiary hydroxyl group at C-11. Their structures were determined by high-resolution electrospray mass spectrometry (HRESIMS), spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Their angiotensin-converting enzyme (ACE) inhibitory activity was reported, and geospallins A⁻C (1⁻3) showed inhibitory activity with IC50 values of 29⁻35 µM.

Keywords: Geosmithia pallida; deep-sea-derived fungus; thiodiketopiperazines.

MeSH terms

  • Angiotensin-Converting Enzyme Inhibitors / chemistry
  • Angiotensin-Converting Enzyme Inhibitors / isolation & purification
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Aquatic Organisms / chemistry*
  • Circular Dichroism
  • Enzyme Assays / methods
  • Hypocreales / chemistry*
  • Inhibitory Concentration 50
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Peptidyl-Dipeptidase A / chemistry*
  • Piperazines / chemistry
  • Piperazines / isolation & purification
  • Piperazines / pharmacology*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Piperazines
  • Peptidyl-Dipeptidase A