Bioactive metabolites from the leaves of <i>Withania adpressa</i> Widad Ben Bakrim Laila El Bouzidi Jean-Marc Nuzillard Sylvian Cretton Noémie Saraux Aymeric Monteillier Philippe Christen Muriel Cuendet Khalid Bekkouche 10.6084/m9.figshare.7356773.v1 https://tandf.figshare.com/articles/journal_contribution/Bioactive_metabolites_from_the_leaves_of_i_Withania_adpressa_i_/7356773 <p><b>Context:</b><i>Withania</i> (Solanaceae) species are known to be a rich source of withanolides, which have shown several biological properties.</p> <p><b>Objective:</b> To identify the compounds responsible for <i>Withania adpressa</i> Coss. antioxidant activity and further test them for their NF-κB inhibition and antiproliferative activity in multiple myeloma cells.</p> <p><b>Materials and methods</b>: Compounds were obtained from the EtOAc extract of <i>W. adpressa</i> leaves. Structure elucidation was carried out mainly by 1D- and 2D-NMR, and mass spectrometry. Isolated compounds were tested in a dose-response for their <i>in vitro</i> NF-κB inhibition and antiproliferative activity in multiple myeloma cells after 5 and 72 h treatment, respectively.</p> <p><b>Results:</b> The fractionation resulted in the isolation of a new glycowithanolide named wadpressine (<b>5</b>) together with withanolide F, withaferin A, coagulin L, and nicotiflorin. The latter showed a moderate ability to scavenge free radicals in DPPH (IC<sub>50</sub> = 35.3 µM) and NO (IC<sub>50</sub> = 41.3 µM) assays. Withanolide F and withaferin A exhibited low µM antiproliferative activity against both multiple myeloma cancer stem cells and RPMI 8226 cells. Furthermore, they inhibited NF-κB activity with IC<sub>50</sub> values of 1.2 and 0.047 µM, respectively. The other compounds showed a moderate inhibition of cell proliferation in RPMI 8226 cells, but were inactive against cancer stem cells and did not inhibit NF-κB activity.</p> <p><b>Discussion and conclusions:</b> One new glycowithanolide and four known compounds were isolated. Biological evaluation data gave further insight on the antitumor potential of withanolides for refractory cancers.</p> 2018-11-18 07:14:05 Withanolides wadpressine antioxidant activity NF-κB inhibition antiproliferative activity