Cytotoxic activity against tumour cell lines and anti-inflammatory effects of compounds isolated from Xylopia aromatica

Plants of the Annonaceae family have been used in traditional medicine for the treatment of a variety of ailments including diarrhoea, fever, pain and inflammation. Bioassay-guided separation of a Xylopia aromatica leaf extract led to the isolation of two labdane diterpenoids whose structures were identified by 1 H, 13C NMR spectroscopy as 8(17),12E,14-labdatrien-18-oic acid (1) and 15,16-dihydroxy-8(17),13(E)-labdadien-19-oic acid (2), These diterpenoids were tested for their cytotoxic effect against the human HT29 and MDA-MB-231, and mouse 4T1 cancer cell lines. Using a 48h sulphorhodamine B assay, compounds 1 and 2 exhibited relatively low GI₅₀ (growth inhibition) values of 9.4 and 7.5 µg/mL respectively, compared to 7.1 µg/mL for cisplatin. The anti-inflammatory effects of the compounds were tested in terms of their ability to inhibit nitric oxide (NO) production by LPS-activated RAW 264.7 macrophages over 24h. These compounds also inhibited NO production at lower concentrations (IC₅₀ values: 1 – 13.5 µg/mL, 2 – 12.3 ug/mL, aminoguanidine [control] – 10.5 µg/mL), but without showing an important cytotoxic effect (IC₅₀ > 200 ug/mL) using the (3-(4,5-dimetiltiazol-2yl) -5- (3-carboximetoxifenil) -2(4-sulfofenil) -2 H-tetrazolium) (MTS) cytotoxicity assay. From the inactive fractions six known compounds were isolated: quercitrin, quercetin 3,3' dirhamnose, liriodenine, lysicamine, xylopianin and annomontacin.