BACE1 Inhibitory Meroterpenoids from Aspergillus terreus

• Published in: Journal of natural products (Washington, D.C.) Vol. 81; no. 9; pp. 1937 - 1945
• Main Authors: Qi, Changxing, Liu, Mengting, Zhou, Qun, Gao, Weixi, Chen, Chunmei, Lai, Yongji, Hu, Zhengxi, Xue, Yongbo, Zhang, Jinwen, Li, Dongyan, Li, Xiao-Nian, Zhang, Qing, Wang, Jianping, Zhu, Hucheng, Zhang, Yonghui
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society and American Society of Pharmacognosy 28.09.2018; Amer Chemical Soc
• Subjects: Amyloid Precursor Protein Secretases - antagonists & inhibitors; Aspartic Acid Endopeptidases - antagonists & inhibitors; Chemistry, Medicinal; Crystallography, X-Ray; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Pharmacology & Pharmacy; Plant Sciences; Science & Technology; Terpenes - chemistry; Terpenes - isolation & purification; Terpenes - pharmacology; ALZHEIMERS-DISEASE; AMYLOID-BETA; BIOSYNTHESIS
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.7b01050

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.