Spiroindole Alkaloids and Spiroditerpenoids from Aspergillus duricaulis and Their Potential Neuroprotective Effects

J Nat Prod. 2015 Nov 25;78(11):2572-9. doi: 10.1021/acs.jnatprod.5b00508. Epub 2015 Oct 30.

Abstract

Six new spiroindole alkaloids (1-6) and two new spiroditerpenoids (7 and 8) were isolated from an EtOAc extract of Aspergillus duricaulis culture media together with five known compounds. The structures of the isolated compounds were elucidated by analysis of NMR and MS data, and the absolute configurations of compounds 1-8 were confirmed by CD spectroscopic methods. All isolated compounds were evaluated for their inhibition of beta-amyloid (Aβ) aggregate-induced toxicity in PC12 cells and Aβ aggregation. Compounds 8-11 efficiently protected PC12 cells against Aβ aggregate-induced toxicity, but only compound 9 inhibited Aβ aggregation. On the other hand, compounds 4 and 5 exhibited moderate inhibitory effects on Aβ aggregation, but did not protect the cells from Aβ aggregate-induced toxicity. Preincubating Aβ monomers with compounds 4 and 5 rescued PC12 cells against Aβ aggregate-induced toxicity by reducing neurotoxic Aβ aggregates. Compound 9 inhibited both Aβ aggregate-induced toxicity and Aβ aggregation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / antagonists & inhibitors
  • Animals
  • Aspergillus / drug effects
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology*
  • Indole Alkaloids / chemistry
  • Indole Alkaloids / isolation & purification*
  • Indole Alkaloids / pharmacology*
  • Molecular Structure
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / isolation & purification*
  • Neuroprotective Agents / pharmacology*
  • Nuclear Magnetic Resonance, Biomolecular
  • PC12 Cells
  • Rats
  • Spiro Compounds / chemistry
  • Spiro Compounds / isolation & purification*
  • Spiro Compounds / pharmacology*

Substances

  • Amyloid beta-Peptides
  • Diterpenes
  • Indole Alkaloids
  • Neuroprotective Agents
  • Spiro Compounds