Withanolides from leaves of cultivated Acnistus arborescens

Abstract

Seven withanolides, including four previously unknown, were isolated from the acetone and ethanol extracts of cultivated specimens of Acnistus arborescens. These four compounds were identified as rel-(18R,22R)-5β,6β:18β,20-diepoxy-3β,18α-dimethoxy-4β-hydroxy-1-oxowith-24-enolide, rel-(20R,22R)-5β,6β-epoxy-4β,16α,20-trihydroxy-1-oxowitha-2,24dienolide, rel-(20R,22R)-16α-acetoxy-6α-chloro-4β,5β,20-trihydroxy-1-oxowitha-2,24-dienolide and rel-(20R,22R)-16α-acetoxy-20-hydroxy-1-oxowitha-2,5,24-trienolide. Their structures were elucidated by interpretation of spectroscopic data (1D and 2D NMR), HRESIMS experiments and comparison with published data for similar compounds. Cytotoxicity of the isolated compounds was evaluated against a panel of four tumor cell lines (HL-60, HCT-116, SF-268 and PANC-1). Withanolide D was the most active, with an IC50 value in the range of 0.3-1.7 μM, rel-(18R,22R)-5β,6β:18β,20-diepoxy-3β,18α-dimethoxy-4β-hydroxy-1-oxowith-24-enolide and rel-(20R,22R)-5β,6β-epoxy-4β,16α,20-trihydroxy-1-oxowitha-2,24dienolide were moderately active, while all the others were non-cytotoxic.

Keywords: Acnistus arborescens; Cytotoxic activity; Solanaceae; Withanolides; Withaphysalins.