Bioassay-Guided Isolation of Antiproliferative Compounds from Grape (Vitis vinifera) Stems

The fractionation, guided by cell-growth inhibition assay, of the EtOAc crude extract from grape stems of the Sicilian Vitis vinifera variety ‘Nerello Mascalese’ allowed identification of ten constituents, isolated either as pure compounds (1, 3–5, 7–10) or inseparable mixtures (2a-d and 6a-e). The pure constituents were: two triterpenoid acids, oleanolic (1) and betulinic acids (5); daucosterol (7); a stilbenoid, E-resveratrol (3) and its dimer E-ε-viniferin (4); the simple phenol gallic acid (8); and the flavanols catechin (9) and gallocatechin (10). Four 6′-O-acyldaucosterols (2a-d) and five 1,2-di-O-acyl-3-O-β-D-galactopyranosyl glycerols (6a-e) were also identified as inseparable mixtures. All the isolated compounds were subjected to spectroscopic analysis and MTT bioassay on MCF-7 human breast cancer cells. The majority showed growth-inhibitory activity, 5 being the most active (GI50 = 0.57 μM). Compounds 3–5 were also tested on HT-29, U-87-MG and U-373-MG cell lines.