Lanostane Triterpenoids and Ergostane Steroids from Ganoderma luteomarginatum and Their Cytotoxicity.

Macrofungus Ganoderma luteomarginatum is one of the main species of Ganoderma fungi distributed in Hainan province of China, the fruiting bodies of which have been widely used in folk as a healthy food to prevent tumors. To explore the potential cytotoxic constituents from G. luteomarginatum, the phytochemical investigation on the ethyl acetate soluble fraction of 95% ethanolic extract from the fruiting bodies of this fungus led to the isolation of twenty-six lanostane triterpenoids (1-26), including three undescribed ones (1-3), together with eight ergostane steroids (27-34). The structures of three new lanostane triterpenoids were elucidated as lanosta-7,9(11)-dien-3ß-acetyloxy-24,25-diol (1), lanosta-7,9(11)-dien-3-oxo-24,26-diol-25-methoxy (2), and lanosta-8,20(22)-dien-3,11,23-trioxo-7ß,15ß-diol-26-oic acid methyl ester (3) by the analysis of 1D, 2D NMR, and HRESIMS spectroscopic data. All isolates were assayed for their cytotoxic activities using three human cancer cell lines (K562, BEL-7402, and SGC-7901) and seven lanostane triterpenoids (1, 2, 7, 13, 18, 22, and 24), and one ergostane steroid (34) showed definite cytotoxicity with IC50 values that ranged from 6.64 to 47.63 µg/mL. Among these cytotoxic lanostane triterpenoids, compounds 2 and 13 showed general cytotoxicity against three human cancer cell lines, while compounds 1 and 18 exhibited significant selective cytotoxicity against K562 cells with IC50 values of 8.59 and 8.82 µg/mL, respectively. Furthermore, the preliminary structure-cytotoxicity relationships was proposed.

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

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 ß-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)-3ß,7ß,15ß-Trihydroxy-11,23-dioxolanost-8,17(20)-dien-26-oate and (20E)-15ß-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 3ß,7ß,15ß-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)-3ß,7ß,15ß-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.

Lanostane triterpenoids from Ganoderma luteomarginatum and their cytotoxicity against four human cancer cell lines.

Lanostane triterpenoids are major metabolites of macrofungi from the genus Ganoderma and possess enormous substitution diversity and remarkable biological activities, especially anticancer, antioxidant, and anti-inflammatory effects. The present phytochemical investigation resulted in the isolation of nine undescribed lanostane triterpenoids and five known analogues from the fruiting bodies of Ganoderma luteomarginatum, which was first phytochemically studied by our group. Chemical structures were elucidated based on spectroscopic evidence. (5α,23E)-27-nor-lanosta-8,23-dien-3,7,25-trione and (5α,23E)-27-nor-3ß-hydroxylanosta-8,23-dien-7,25-dione are undescribed triterpenoids with an unusual 27-nor-lanostane carbon skeleton. All isolates were assayed for their cytotoxic activities using four human cancer cell lines (HGC-27, HeLa, A549, and SMMC-7721) and one human normal cell line (LO2), and the structure-cytotoxicity relationships were preliminarily explored. (5α,24E)-3ß-acetoxyl-26-hydroxylanosta-8,24-dien-7-one exhibited the highest cytotoxicity against HeLa and A549 cell lines, with IC50 values of 1.29 and 1.50 µM, respectively.