Cytotoxic Xanthones from Hypericum stellatum, an Ethnomedicine in Southwest China

Abstract

Hypericum stellatum, a species endemic to China, is used to treat hepatitis by several ethnic groups in Guizhou Province. This research was inspired by the traditional medicinal usage of H. stellatum, and aims to explore the phytochemistry and bioactivity of H. stellatum to explain why local people in Guizhou widely apply H. stellatum for liver protection. In this study, two new prenylated xanthones, hypxanthones A (8) and B (9), together with seven known compounds, were isolated from the aerial parts of the plant. Spectroscopic data as well as experimental and calculated ECD spectra were used to establish the structures of these compounds. Six xanthones isolated in this study, together with four xanthones previously isolated from H. stellatum, were evaluated for their growth-inhibitory activities against five human liver carcinoma cell lines to analyze the bioactivity and structure-activity relationship of xanthones from H. stellatum. Isojacareubin (6) showed significant cytotoxicity against five human liver carcinoma cell lines, with an IC50 value ranging from 1.41 to 11.83 μM, which was stronger than the positive control cisplatin (IC50 = 4.47–20.62 μM). Hypxanthone B (9) showed moderate cytotoxicity to three of the five cell lines. Finally, structure-activity analysis revealed that the prenyl and pyrano substituent groups of these xanthones contributed to their cytotoxicity.

<p>Anti-Tumor Xanthones from <em>Garcinia nujiangensis</em> Suppress Proliferation, and Induce Apoptosis via PARP, PI3K/AKT/mTOR, and MAPK/ERK Signaling Pathways in Human Ovarian Cancers Cells</p>

“…The two known compounds, named isojacareubin (2) 24 and 1,5,6-trihydroxy-2-prenyl-6′,6′-dimethyl-2H-pyrano (2′,3′:3,4)xanthone (3) 27 were identified by comparison of spectroscopic data with reported values. Isojacareubin was isolated from Garcinia livingstonei, 28 Garcinia Fusca, 29 and Hypericum stellatum, 30 in the family Clusiaceae; and showed inhibitory effects on hepatocellular carcinoma via protein kinase C in vitro and in vivo. 31…”

Hyperpatone A, a polycyclic polyprenylated acylphloroglucinol with a rare 8/6/5/6/5 pentacyclic skeleton from Hypericum patulum

“…1 There are 64 species of Hypericum in southwest China and most of these plants are ethnomedicinal plants. 2,3 In addition, a variety of chemical constituents, including polycyclic polyprenylated acylphloroglucinols (PPAPs), xanthones, flavonoids, and terpenoids, were reported from Hypericum. 4–6 Among them, PPAPs with fascinating structures and good bioactivity have attracted continuing attention in the areas of natural product chemistry, synthetic chemistry, and pharmacology.…”

“…11 In recent years, ultraperformance liquid chromatographyelectrospray ionization-mass spectrometry (UPLC-ESI-MS) has become a useful tool for detecting and isolating trace components in a complex mixture of plant extracts. 12 Thus, in our systematic study of novel and bioactive PPAPs, 13,14 a trace highly oxidated PPAP (1) as well as a biosynthesis-related PPAP (2) was isolated from H. patulum using UPLC-MS/MS guided isolation. Compound 1 represents the first PPAP with an unprecedented 8/6/5/6/5 pentacyclic skeleton and an intramolecular peroxy bridge, which might be derived from the [3.3.1]-type bicyclic polyprenylated acylphloroglucinol via the critical Baeyer-Villiger oxidation, decarboxylation, and intramolecular cyclization.…”

Synthesis and Molecular Docking Studies of Alkoxy- and Imidazole-Substituted Xanthones as α-Amylase and α-Glucosidase Inhibitors

“…The functionalization of xanthones as α-glucosidase inhibitors has revealed the key factors involved in their observed inhibitory activity: the formation of an H-bond, The functionalization of xanthones as α-glucosidase inhibitors has revealed the key factors involved in their observed inhibitory activity: the formation of an H-bond, hy-drophobic groups with a π-conjugated system, and flexibility in conformation [21,26]. This is the case of 2-hydroxy-3-methoxyxanthone 1 (Figure 1), a natural product found in plants of the genus Hypericum (Clusiaceae), which exhibits anticancer properties [27][28][29]. Thus, it would be interesting to use this compound as a molecular platform to generate new derivatives with potential pharmaceutical applications.…”