New 21-nordammarane saponins with anti-inflammatory and cytotoxic activities from Lavigeria macrocarpa Oliv

Abstract

Chemical investigation of the ethanol extract from the stems and roots of the medicinal plant Lavigeria macrocarpa led to the isolation and structure elucidation of three previously unreported 21-nordammarane-type saponins namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-[α-L-rhamnopyranosyl-(1→2)-β-D-glucopyranoside] (1), 6α,27-dihydroxy-3-oxo-21-nordammar-24-(Z)-ene 27-O-β-D-glucopyranoside (2), and 2α,3β,6α,27-tetrahydroxy-21-nordammar-24-(Z)-ene 27-O-β-D-glucopyranoside (3) trivially named lavigemacrocarposide A-C, along with eight known secondary metabolites. Acid hydrolysis of lavigemacrocarposide A yielded a new prosapogenin namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-β-D-glucopyranoside (1a) and the previously unreported artefactual aglycones 1b and 1c. Their structures were elucidated by spectroscopic analyses including mass spectrometry, 1D and 2D NMR as well as chemical evidence. The EtOH extract, some isolated compounds as well as the prosapogenin (1a) and compounds 1b and 1c were evaluated for anti-inflammatory and cytotoxic activity. Icacine (5) exhibited a significant cytotoxicity against both HeLa and MCF-7 cell lines with an IC₅₀ value of 0.78 μg/mL. All the tested compounds showed more that 50% inhibition of NO production, except for 1 and 2.

Keywords: 21-nordammarane saponins; Cytotoxic and anti-inflammatory activities; Icacinaceae; Lavigeria macrocarpa; Pimarane diterpenoids.