Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum

	Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum
	Guo, Yi 1; Zhang, Na 1; Sun, Weiguang 1; Duan, Xueyan 1; Zhang, Qing 1; Zhou, Qun 1; Chen, Chunmei 1; Zhu, Hucheng 1; Luo, Zengwei 1; Liu, Junjun 1; Li, Xiao-Nian 2; Xue, Yongbo 1; Zhang, Yonghui 1
	2018-11-21
发表期刊	ORGANIC & BIOMOLECULAR CHEMISTRY
ISSN	1477-0520
卷号	16 期号:43 页码:8130-8143
摘要	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, Rh-2(OCOCF3)(4)- and [Mo-2(OAc)(4)]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of C-13 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 -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 M) and simultaneously inhibited BACE1 (at a concentration of 5 M) 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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/63165
专题	植物化学与西部植物资源持续利用国家重点实验室
通讯作者	Xue, Yongbo; Zhang, Yonghui
作者单位	1.Huazhong Univ Sci & Technol, Sch Pharm, Tongji Med Coll, Hubei Key Lab Nat Med Chem & Resource Evaluat, Wuhan 430030, Hubei, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, Kunming 650204, Yunnan, Peoples R China
推荐引用方式 GB/T 7714	Guo, Yi,Zhang, Na,Sun, Weiguang,et al. Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2018,16(43):8130-8143.
APA	Guo, Yi.,Zhang, Na.,Sun, Weiguang.,Duan, Xueyan.,Zhang, Qing.,...&Zhang, Yonghui.(2018).Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum.ORGANIC & BIOMOLECULAR CHEMISTRY,16(43),8130-8143.
MLA	Guo, Yi,et al."Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum".ORGANIC & BIOMOLECULAR CHEMISTRY 16.43(2018):8130-8143.