BACE1 Inhibitory Meroterpenoids from Aspergillus terreus

October 11, 2018

Title

BACE1 Inhibitory Meroterpenoids from Aspergillus terreus

Author

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

Year

2018

Journal

Journal of Natural Products

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 IC50values of 3.3, 5.9, and 31.7 μM, respectively.

Instrument

J-810

Keywords

Circular dichroism, Absolute configuration, Medicinal, Natural products