Title
Isolation of eudesmanes from Pluchea odorata and evaluation of their effects on cancer cell growth and tumor invasiveness in vitro
Author
Michael Blaschke, Martin Zehl, Beatrix Hartl, Claudia Strauß, Johannes Winkler, Ernst Urban, Georg Krupitza, Brigitte Kopp
Year
2017
Journal
Phytochemistry
Abstract
The traditionally used Central American medicinal plant Pluchea odorata, known as an anti-inflammatory and cancer cell growth-inhibiting remedy, was subjected to bioassay-guided isolation. Structure elucidation by 1D- and 2D-NMR and MS techniques supported by ECD and UV spectroscopic data revealed seven structurally previously undescribed and eight known eudesmane-type sesquiterpenes. Furthermore, one previously undescribed and one known phytol-like alcohol were identified. All compounds were tested for their cytotoxicity in cancer cells and for their anti-invasive effects. Among the eudesmanes, 3α-(2′,3′-epoxy-2′-methylbutyryloxy)-4α-hydroxy-11-hydroperoxy-eudesm-6-en-8-one exhibited the most potent cytotoxic activity with an IC50value of 8.8 μM (after 48 h). Also in an in vitro model measuring the tumor-triggered breaching of the adjacent lymph endothelial cell barrier (3S*,4R*,5S*,10S*,2′R*,3′R*)-3-(2′,3′-epoxy-2′-methylbutyryloxy)-4,7-dihydroxy-eudesm-11-en-8-one (IC75 = 47 μM) and (3S*,4R*,5R*,10S*,2′R*,3′R*)-3-(2′,3′-epoxy-2′-methylbutyryloxy)-4-acetyloxy-6-methoxy-11-hydroxy-eudesm-6-en-8-one (IC75 = 73 μM) showed inhibitory activities. Furthermore, preliminary structure-activity relationships (SARs) of the eudesmanes were developed.
Instrument
J-810
Keywords
Circular dichroism, Stereochemistry, Natural products, Pharmaceutical