Bioactive metabolites from the leaves of withania adpressa

Abstract

Context: Withania (Solanaceae) species are known to be a rich source of withanolides, which have shown several biological properties. Objective: To identify the compounds responsible for Withania adpressa Coss. antioxidant activity and further test them for their NF-jB inhibition and antiproliferative activity in multiple myeloma cells. Materials and methods: Compounds were obtained from the EtOAc extract of W. adpressa 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 in vitro NF-jB inhibition and antiproliferative activity in multiple myeloma cells after 5 and 72 h treatment, respectively. Results: The fractionation resulted in the isolation of a new glycowithanolide named wadpressine (5) together with withanolide F, withaferin A, coagulin L, and nicotiflorin. The latter showed a moderate ability to scavenge free radicals in DPPH (IC50 ¼ 35.3 mM) and NO (IC50 ¼ 41.3 mM) assays. Withanolide F and withaferin A exhibited low mM antiproliferative activity against both multiple myeloma cancer stem cells and RPMI 8226 cells. Furthermore, they inhibited NF-jB activity with IC50 values of 1.2 and 0.047 mM, 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-jB activity. Discussion and conclusions: One new glycowithanolide and four known compounds were isolated. Biological evaluation data gave further insight on the antitumor potential of withanolides for refractory cancers.