Methylated Xanthones from the Rootlets of <i>Metaxya rostrata</i> Display Cytotoxic Activity in Colorectal Cancer Cells

• Main Authors: Eva Mittermair, Hanspeter Kählig, Ammar Tahir, Stefanie Rindler, Xenia Hudec, Hemma Schueffl, Petra Heffeter, Brigitte Marian, Liselotte Krenn
• Format: Article
• Language: English
• Published: MDPI AG 2020-09-01
• Series: Molecules
• Subjects: <i>Metaxya rostrata</i>; metaxyaceae; 2-deprenyl-6-<i>O</i>-methyl-7-hydroxy-rheediaxanthone B; 2-deprenyl-5-<i>O</i>-methyl-7-methoxy-rheediaxanthone B; 2-deprenyl-5-<i>O</i>-methyl-7-hydroxy-rhee-diaxanthone B; 2-deprenyl-7-methoxy-rheediaxanthone B
• Online Access: https://www.mdpi.com/1420-3049/25/19/4449

The tree fern <i>Metaxya rostrata</i> (Kunth) C. Presl is common in the rainforests of Central and South America, where suspensions of the dried rhizome are traditionally used to treat intestinal diseases. Two compounds from this plant, 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone B (OH-XB), have been shown to be biologically highly active against colorectal cancer (CRC) cells in previous studies. The current investigation resulted in the isolation of the previously undescribed methylated xanthones 2-deprenyl-6-<i>O</i>-methyl-7-hydroxy-rheediaxanthone B, 2-deprenyl-5-<i>O</i>-methyl-7-methoxy-rheediaxanthone B, 2-deprenyl-5-<i>O</i>-methyl- 7-hydroxy-rheediaxanthone B and 2-deprenyl-7-methoxy-rheediaxanthone B. All compounds were isolated by column chromatography, structures were elucidated by one- and two-dimensional NMR-experiments and the identities of the compounds were confirmed by LC-HRMS. In logarithmically growing SW480 CRC cell cultures, cytotoxicity by neutral red uptake and MTT assays as well as caspase activation was analyzed. Cellular targets were examined by Western blot, and topoisomerase I (topo I) inhibition potential was tested. Comparing the structure-activity relationship with XB and OH-XB, the monomethylated derivatives showed qualitatively similar effects/mechanisms to their nonmethylated analogues, while dimethylation almost abolished the activity. Inhibition of topo I was dependent on the presence of an unmethylated 7-OH group.