Inhibition of BACE1 and Amyloid-β Aggregation by Meroterpenoids from the Mushroom Albatrellus yasudae

Abstract

To develop drugs to treat Alzheimer’s disease (AD) on the basis of the amyloid cascade hypothesis, the amyloid-β (Aβ) aggregation inhibitory activities of 110 extracts from mushrooms were evaluated by thioflavin T (Th-T) assays. The MeOH extract of Albatrellus yasudae inhibited Aβ aggregation, and the bioactivity-guided fractionation of the extract afforded four novel meroterpenoids, named scutigeric acid (1), albatrelactone methyl ester (2), albatrelactone (3), and 10′,11′-dihydroxygrifolic acid (4), together with two known compounds, grifolin (5) and grifolic acid (6). The structures of 1–4 were elucidated using NMR, MS, UV, IR, and induced ECD spectral data. The structure of 1 was determined as a methyl ester (1a) by 2D NMR spectroscopy. Th-T assays showed that compounds 1–4 and 1a possessed inhibitory activities against Aβ aggregation, with IC50 values of 6.6, 40.7, 51.4, 53.3, and 50.3 μM, respectively. Notably, 1 possessed an inhibitory activity against Aβ aggregation comparable to that of myricetin as a positive control. Moreover, 1–6 exhibited inhibitory activities against BACE1, with IC50 values of 1.6, 10.9, 10.5, 34.4, 6.1, and 1.4 μM, respectively.

Synthetic Biology-Based Discovery of Diterpenoid Pyrones from the Genome of Eupenicillium shearii

“…Some meroterpenoids, including fungal DPs, have been reported to inhibit aggregation of Aβ in vitro. ,− Thus, we evaluated the inhibitory activity of compounds 1 – 9 on Aβ42 aggregation, and most of them, especially 4 , 7 , and 8 , moderately suppressed aggregation after incubation for 24 h (Figure ).…”

Computational methods and points for attention in absolute configuration determination

“…The method of determining the AC of diols is to use dimolybdenum methodology with dimolybdenum tetracarboxylates which act as auxiliaries (Jawiczuk et al, 2014;Masuda et al, 2021). This consists of the in situ formation of chiral complexes (Mo 2 -core).…”

Natural sesquiterpene quinone/quinols: chemistry, biological activity, and synthesis

“…myricetin = 2.8 mM). 149,150 Cochlearoid A (280) has potent activity toward Cav3.1 TTCC through channel gating modulation (IC 50 = 11.4 mM, Hill coefficient = 1.6; IC 50 of pos. mibefradil = 10.4 mM, Hill coefficient = 1.6), indicating its possible application in neurological disorders.…”