Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum

Qi-Qi Wang; Xiao-Dong Wang; Ling-Zhi Wu; Qiang-Qiang Fang; Ya-Nan Liu; Kun Jiang; Shi-Jin Qu; Chang-Heng Tan

doi:10.1016/j.fitote.2020.104678

Polyprenylated acylphloroglucinols as deubiquitinating protease USP7 inhibitors from Hypericum hookerianum

Fitoterapia. 2020 Oct:146:104678. doi: 10.1016/j.fitote.2020.104678. Epub 2020 Jun 25.

Authors

Qi-Qi Wang¹, Xiao-Dong Wang², Ling-Zhi Wu³, Qiang-Qiang Fang¹, Ya-Nan Liu¹, Kun Jiang⁴, Shi-Jin Qu⁵, Chang-Heng Tan⁶

Affiliations

¹ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China.
² Institute of Hospital Management, West China Hospital, Sichuan University, Chengdu 610041, China.
³ State Key Laboratory of Proteomics, National Center for Protein Sciences (Beijing)，Beijing Proteome Research Center, Beijing Institute of Lifeomics, Beijing 102206, China.
⁴ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁵ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: sjqu@simm.ac.cn.
⁶ Department of Natural Medicinal Chemistry, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; School of Pharmacy, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: chtan@simm.ac.cn.

PMID: 32593692
DOI: 10.1016/j.fitote.2020.104678

Abstract

Hookerianones A - E (1-5), five new polyprenylated acylphloroglucinols (PPAPs), along with six known ones, were isolated from the aerial parts of Hypericum hookerianum. Their structures were elucidated by analyses of MS, NMR, chiroptical properties, biogenetic pathway, and/or single crystal X-ray diffraction. A ubiquitin-rhodamine 110 assay showed that furohyperforin and hypercalin C, two representative PPAPs in this plant, inhibited more than 90% USP7 at the concentration of 10 μM.

MeSH terms

China
Hypericum / chemistry*
Molecular Structure
Phloroglucinol / isolation & purification
Phloroglucinol / pharmacology*
Phytochemicals / isolation & purification
Phytochemicals / pharmacology
Plant Components, Aerial / chemistry
Protease Inhibitors / isolation & purification
Protease Inhibitors / pharmacology*
Ubiquitin-Specific Peptidase 7 / antagonists & inhibitors*

Substances

Phytochemicals
Protease Inhibitors
Phloroglucinol
Ubiquitin-Specific Peptidase 7