Screening for Anti‐Aβ Aggregation Activity of Marine Fungal Natural Products Based on a Gold Nanoparticle Method

Screening Aβ aggregation inhibitors (AAIs) is important for Alzheimer's disease drug discovery. However, common cellular or biochemical methods are not suitable for high-throughput natural product screening. A gold nanoparticle (GNP) screening method was employed in this study to screen marine fungal crude extracts and pure compounds for quick AAI discovering. The anti-Aβ aggregation activity was further inspected using transmission electron microscopic (TEM) observation, and the interaction between active molecules and different Aβ species was revealed by molecular docking. The results indicated that the fungal extracts DLS2008001(M), BM3T2(M), DLEN2008005(M), TBG1-16(P), and TBG1-13(P) showed activity comparable to the positive control human serum albumin at the concentration of 500 µg/mL; 10 pure compounds also displayed moderate anti-aggregation activity, particularly nidulin, aspergillusidone G, and butyrolactone I. The inspection of anti-Aβ aggregation effect through TEM further demonstrated that extracts TBG1-16(P), DLS2008001(M), and BM3T2(M) dramatically inhibited the formation of Aβ aggregates. Molecular docking displayed low binding energies and key interactions of nidulin, aspergillusidone G, and butyrolactone I, with nine types of Aβ peptides. These findings indicate that the GNP method is efficient in screening AAIs and reveal marine fungal natural products as valuable sources of small molecular AAIs.