BACE1 Inhibitory Meroterpenoids from Aspergillus terreus.

BACE1 Inhibitory Meroterpenoids from Aspergillus terreus.

Author:

Qi C, Liu M, Zhou Q, Gao W, Chen C, Lai Y, Hu Z, Xue Y, Zhang J, Li D, Li XN, Zhang Q, Wang J, Zhu H, Zhang Y.

Date: 6 February 2019

Abstract:

Sixteen 3,5-dimethylorsellinic acid-based (DMOA-based) meroterpenoids, including 10 new compounds, asperterpenes D-M (1-10), were obtained from Aspergillus terreus. The structures and absolute configurations of the new compounds were confirmed by extensive spectroscopy, single-crystal X-ray diffraction analysis, and experimental electronic circular dichroism (ECD) measurements. Compounds 2, 3, and 7 are the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing a unique cis-fused A/B ring system. These new compounds were evaluated for their inhibitory activity against β-site amyloid precursor protein-cleaving enzyme 1 (BACE1). Compounds 2, 3, and 7, the first 3,5-dimethylorsellinic acid-based meroterpenoids possessing cis-fused A/B rings, exhibited significant inhibitory activities against BACE1 with IC50 values of 3.3, 5.9, and 31.7 μM, respectively.

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