Polycyclic polyprenylated acylphloroglucinol congeners from Garcinia yunnanensis Hu with inhibitory effect on α-hemolysin production in Staphylococcus aureus

Dan Zheng; Yuyu Chen; Shijie Wan; Jiaming Jiang; Simin Chen; Changwu Zheng; Hua Zhou; Gang Xu; Hong Zhang; Hongxi Xu

doi:10.1016/j.bioorg.2021.105074

Polycyclic polyprenylated acylphloroglucinol congeners from Garcinia yunnanensis Hu with inhibitory effect on α-hemolysin production in Staphylococcus aureus

Bioorg Chem. 2021 Sep:114:105074. doi: 10.1016/j.bioorg.2021.105074. Epub 2021 Jun 9.

Authors

Dan Zheng¹, Yuyu Chen², Shijie Wan², Jiaming Jiang², Simin Chen², Changwu Zheng², Hua Zhou³, Gang Xu⁴, Hong Zhang⁵, Hongxi Xu⁶

Affiliations

¹ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China; Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
² School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
³ Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
⁴ State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, China.
⁵ School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: zhnjau19851010@163.com.
⁶ Institute of Cardiovascular Disease of Integrated Traditional Chinese and Western Medicine, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: xuhongxi88@gmail.com.

PMID: 34174629
DOI: 10.1016/j.bioorg.2021.105074

Abstract

α-Hemolysin (Hla) is an extracellular protein secreted by methicillin-resistant Staphylococcus aureus (MRSA) strains that plays a critical role in the pathogenesis of pulmonary, intraperitoneal, intramammary, and corneal infections, rendering Hla a potential therapeutic target. In this study, 10 unreported polycyclic polyprenylated acylphloroglucinol (PPAP) derivatives, garciyunnanins C-L (1-10), with diverse skeletons, were isolated from Garcinia yunnanensis Hu. The structures of these new compounds were determined by HRMS, NMR, electronic circular dichroism (ECD) calculations, single-crystal X-ray diffraction, and biomimetic transformation. Garciyunnanins C and D (1 and 2) were found to be potent Hla inhibitors in the anti-virulence efficacy evaluation against MRSA strain.

Keywords: Garcinia yunnanensis Hu; Polycyclic polyprenylated acylphloroglucinols (PPAPs); Staphylococcus aureus; α-Hemolysin (Hla).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / pharmacology*
Bacterial Toxins / antagonists & inhibitors*
Bacterial Toxins / biosynthesis
Dose-Response Relationship, Drug
Garcinia / chemistry*
Hemolysin Proteins / antagonists & inhibitors*
Hemolysin Proteins / biosynthesis
Microbial Sensitivity Tests
Molecular Structure
Phloroglucinol / chemistry
Phloroglucinol / isolation & purification
Phloroglucinol / pharmacology*
Staphylococcus aureus / drug effects*
Staphylococcus aureus / metabolism
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Bacterial Toxins
Hemolysin Proteins
staphylococcal alpha-toxin
Phloroglucinol