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 (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.