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

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 (A beta) aggregate-induced toxicity in PC12 cells and A beta aggregation. Compounds 8-11 efficiently protected PC12 cells against A beta aggregate-induced toxicity, but only compound 9 inhibited A beta aggregation. On the other hand, compounds 4 and 5 exhibited moderate inhibitory effects on A beta aggregation, but did not protect the cells from A beta aggregate-induced toxicity. Preincubating A beta monomers with compounds 4 and 5 rescued PC12 cells against A beta aggregate-induced toxicity by reducing neurotoxic A beta aggregates. Compound 9 inhibited both A beta aggregate-induced toxicity and A beta aggregation.