Twelve undescribed derivatives of ganoderic acid isolated from Ganoderma luteomarginatum and their cytotoxicity against three human cancer cell lines

• Published in: Phytochemistry (Oxford) 2021-03, Vol.183, p.112617-112617, Article 112617
• Main Authors: Li, Xiao-Cui, Liu, Fei, Su, Hai-Guo, Peng, Cheng, Zhou, Qin-Mei, Liu, Juan, Huang, Yuan-Jin, Guo, Li, Xiong, Liang
• Format: Article
• Language: English
• Subjects: Cell Line; Cytotoxicity; Ganoderic acid derivatives; Ganoderma; Ganoderma luteomarginatum; Ganodermataceae; Humans; Lanostane triterpenoids; Molecular Structure; Neoplasms; Triterpenes - pharmacology
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2020.112617

Lanostane triterpenoids are thought to be the main underlying preclinical antitumor secondary metabolites of the genus Ganoderma. To further explore the potential cytotoxic triterpenoids from Ganoderma luteomarginatum, the ethyl acetate soluble fraction of 95% ethanolic extract was systematically studied. Twelve previously undescribed lanostane-type triterpene acids were isolated from the fruiting bodies of G. luteomarginatum, and their structures were elucidated by extensive spectroscopic analyses. Among them, 11 compounds have an unusual β-configuration for OH-15. All isolates were assessed for cytotoxic activities using three human cancer cell lines (A549, HGC-27, and SMMC-7721) and one human normal cell line (LO2). (17Z)-3β,7β,15β-Trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate and (20E)-15β-hydroxy-3,7,11,23-tetraoxolanost-20(22)-en-26-oate exhibited significant selective cytotoxicity against HGC-27 cells and A549 cells, respectively, with IC50 values of 6.82 ± 0.77 and 13.67 ± 1.04 μM, while 3β,7β,15β-trihydroxy-11,23-dioxolanost-8-en-26-oate inhibited the proliferation of both A549 and SMMC-7721 cells. In addition, Hoechst fluorescence 33,258 staining and Annexin V-FITC/PI double staining proved that (17Z)-3β,7β,15β-trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate could induce apoptosis in HGC-27 cells. Furthermore, a comparison of the results in this study and previous literature demonstrated that ganoderic alcohols have stronger cytotoxicity than the corresponding derivatives of ganoderic acid in the genus Ganoderma. [Display omitted] •Twelve new derivatives of ganoderic acid were isolated from G. luteomarginatum.•Compounds 1 and 2 are cis and trans isomers with a rare double bond (Δ17,20).•Compound 1 exhibited significant selective cytotoxicity against HGC-27 cells.•Compound 8 selectively inhibited the proliferation of A549 cells.•Ganoderic alcohols have stronger cytotoxicity than the derivatives of ganoderic acid.