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

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