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Issue 43, 2018
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Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum

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Abstract

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 β-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.

Graphical abstract: Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum

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Publication details

The article was received on 23 Aug 2018, accepted on 05 Oct 2018 and first published on 08 Oct 2018


Article type: Paper
DOI: 10.1039/C8OB02067A
Citation: Org. Biomol. Chem., 2018,16, 8130-8143
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    Bioactive polycyclic polyprenylated acylphloroglucinols from Hypericum perforatum

    Y. Guo, N. Zhang, W. Sun, X. Duan, Q. Zhang, Q. Zhou, C. Chen, H. Zhu, Z. Luo, J. Liu, X. Li, Y. Xue and Y. Zhang, Org. Biomol. Chem., 2018, 16, 8130
    DOI: 10.1039/C8OB02067A

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