Anti-BACE1 and anti-AchE activities of undescribed spiro-dioxolane-containing meroterpenoids from the endophytic fungus Aspergillus terreus Thom

Publication date: September 2019Source: Phytochemistry, Volume 165Author(s): Changxing Qi, Qun Zhou, Weixi Gao, Mengting Liu, Chunmei Chen, Xiao-Nian Li, Yongji Lai, Yuan Zhou, Dongyan Li, Zhengxi Hu, Hucheng Zhu, Yonghui ZhangAbstractSpiroterreusnoids A–F, six undescribed spiro-dioxolane-containing adducts bearing 3,5-dimethylorsellinic acid-based meroterpenoid and 2,3-butanediol moieties were isolated from the endophytic fungus Aspergillus terreus Thom from Tripterygium wilfordii Hook. f. (Celastraceae). The structures of these adducts were established by spectroscopy, single-crystal X-ray diffraction, and experimental electronic circular dichroism (ECD) measurements. Spiroterreusnoids A–F represent the first examples of adducts composed of 3,5-dimethylorsellinic acid-based meroterpenoids. It is noteworthy that spiroterreusnoids A–F possessing a spiro-dioxolane moiety exhibited potential abilities in inhibiting BACE1 (IC50 values ranging from 5.86 to 27.16 μM) and AchE (IC50 values ranging from 22.18 to 32.51 μM), while the other analogues without this fragment displayed no such activities. Taken together, spiroterreusnoids A–F represent the first multitargeted natural adducts that could inhibit BACE1 and AchE, and might provide a new template for the development of new anti-Alzheimer's disease drugs.Graphical abstract
Source: Phytochemistry - Category: Chemistry Source Type: research