The Metabolites With Anti-Alzheimer’s Disease Activity From A Fungal Strain Nodulisporium Sp. Cultivated In Pdb

Alzheimer’s disease(AD) is an age-related, progressive neurodegenerative disorder, which is characterized by the deposition of the amyloid-β peptide(Aβ) in the form of senile plaques. According to the amyloid hypothesis, the accumulation of Aβ plays an important role in the development of AD. Our previous chemical investigation of an endolichenic fungus Nodulisporium sp.(No.65-12-7-1) showed that demethoxyviridin possessed potent anti-Aβ42 aggregation activity in the thioflavin T(Th T) assay. In order to obtain more viridins and to investigate their anti-AD effects, the futher chemical investigation of the fungus was carried out.Twenty-two new compounds(1–22), including eight viridins(1–8), eleven 4-methyl-progesteroids(9–19), and three α-pyrones(20–22) were isolated from the extract of Nodulisporium sp.(No. 65-12-7-1) that was fermented with potato-dextrose-broth(PDB). The structures of the isolated compounds were elucidated by analysis of the detailed spectroscopic data.The Aβ42 aggregation inhibitory activities of the isolated viridins(1?8) were evaluated using a Th T assay. Nodulisporiviridin G(7) displayed potent inhibitory activity with an IC50 value of 1.2 μM. The short-term memory assay on an Aβ transgenic drosophila model of AD showed that all eight viridins(1–8) potently improved the short-term memory capacity.In addition, the antimicrobial activities of compounds 20–22 against Staphylococcus aureus 209 P, Escherichia coli ATCC0111, Aspergillus niger R330, and Candida albicans FIM709 were evaluated using a paper disk diffusion method, and compounds 20–22 exhibited antifungal activities against A. niger R330 and C. albicans FIM709, but no compound showed antibacterial activities against S. aureus 209 P or E. coli ATCC0111.The HPLC characteristic chromatogram of the extract of No. 65-12-7-1 was established, and the major peaks in the characteristic chromatogram were identified unambiguously by comparing with the retention times of compounds isolated from No. 65-12-7-1.