American Chemical Society
np7b01050_si_002.cif (1.18 MB)

BACE1 Inhibitory Meroterpenoids from Aspergillus terreus

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posted on 2018-09-12, 14:40 authored by Changxing Qi, Mengting Liu, Qun Zhou, Weixi Gao, Chunmei Chen, Yongji Lai, Zhengxi Hu, Yongbo Xue, Jinwen Zhang, Dongyan Li, Xiao-Nian Li, Qing Zhang, Jianping Wang, Hucheng Zhu, Yonghui Zhang
Sixteen 3,5-dimethylorsellinic acid–based (DMOA-based) meroterpenoids, including 10 new compounds, asperterpenes D–M (110), 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.