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Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum.
Guo, Yi; Zhang, Na; Sun, Weiguang; Duan, Xueyan; Zhang, Qing; Zhou, Qun; Chen, Chunmei; Zhu, Hucheng; Luo, Zengwei; Liu, Junjun; Li, Xiao-Nian; Xue, Yongbo; Zhang, Yonghui.
Afiliação
  • Guo Y; Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, People's Republic of China. yongboxue@mail.hust.edu.cn zhangyh@mails.tjmu.edu.cn.
Org Biomol Chem ; 16(43): 8130-8143, 2018 11 07.
Article em En | MEDLINE | ID: mdl-30334059
Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A-O (1-15), along with 3 structurally related analogues (16-18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh2(OCOCF3)4- and [Mo2(OAc)4]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC50 6.9-9.2 µM) and simultaneously inhibited BACE1 (at a concentration of 5 µM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Floroglucinol / Compostos Policíclicos / Inibidores da Colinesterase / Hypericum / Prenilação Idioma: En Revista: Org Biomol Chem Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Floroglucinol / Compostos Policíclicos / Inibidores da Colinesterase / Hypericum / Prenilação Idioma: En Revista: Org Biomol Chem Ano de publicação: 2018 Tipo de documento: Article