Secondary Metabolites from the Leather Coral-Derived Fungal Strain Xylaria sp. FM1005 and Their Glycoprotein IIb/IIIa Inhibitory Activity

J Nat Prod. 2021 Feb 26;84(2):466-473. doi: 10.1021/acs.jnatprod.0c01330. Epub 2021 Jan 25.

Abstract

Five new tyrosine derivatives (1-5), one new phenylacetic acid derivative (6), two new quinazolinone analogues (7 and 8), one new naphthalenedicarboxylic acid (9), and one new 3,4-dihydroisocoumarin derivative (10), together with seven known compounds, were isolated from the fungus Xylaria sp. FM1005, which was isolated from Sinularia densa (leather coral) collected in the offshore region of the Big Island, Hawaii. The structures of compounds 1-10 were elucidated by extensive analysis of NMR spectroscopy, HRESIMS, and ECD data. Due to their structure similarity to the antiplatelet drug tirofiban, compounds 1-5 together with 6 were investigated for their antithrombotic activities. Compounds 1 and 2 strongly inhibited the binding of fibrinogen to purified integrin IIIb/IIa in a dose-dependent manner with the IC50 values of 0.89 and 0.61 μM, respectively, and compounds 1 and 2 did not show any cytotoxicity against A2780 and HEK 293 at 40 μM.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anthozoa / microbiology*
  • Cell Line, Tumor
  • Fibrinolytic Agents / isolation & purification
  • Fibrinolytic Agents / pharmacology*
  • HEK293 Cells
  • Hawaii
  • Humans
  • Male
  • Molecular Structure
  • Phenylacetates / isolation & purification
  • Phenylacetates / pharmacology
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors*
  • Quinazolinones / isolation & purification
  • Quinazolinones / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Secondary Metabolism
  • Tyrosine / isolation & purification
  • Tyrosine / pharmacology
  • Xylariales / chemistry*

Substances

  • Fibrinolytic Agents
  • Phenylacetates
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Quinazolinones
  • Tyrosine
  • phenylacetic acid