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Published on: March 15, 2012
BACE1 Inhibitory Meroterpenoids from Aspergillus terreus
Changxing Qi1, Mengting Liu1, Qun Zhou1
1Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, Tongji Medical College , Huazhong University of Science and Technology , Wuhan , Hubei Province 430030 , People's Republic of China.
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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