Isolation of cytotoxic neolignans from Saururus cernuus L. (Saururaceae) using ionic liquid in the microwave assisted extraction (MAE)

Abstract

In the present work, dried leaves of Saururus cernuus (Saururaceae) were subjected to extraction using an ionic liquid (1-butyl-3-methylimidazolium bromide - BMImBr) in the microwave assisted extraction (MAE). The obtained extract was partitioned using n-hexane and cytotoxicity activity of this organic phase against murine melanoma cell line (B16F10-Nex2) was evaluated in vitro. Since this extract displayed activity (100% of cell death at 200 µg mL-1) it was subjected to a bioactivity-guided fractionation to afford four related neolignans: threo-austrobailignan-5 (1), threo-austrobailignan-6 (2), threo-dihydroguaiaretic acid (3) and saucernetin (4). Their chemical structures were established based on NMR and MS spectral analysis. Among the isolated neolignans, compound 2 exhibited the highest cytotoxic activity against HeLa (human cervical melanoma) cells with IC50 of 28.3 ± 3.9 µg mL-1 (86 ± 12 µmol L-1). Furthermore, compounds 2 and 3 exhibited the highest cytotoxic activity against A2058 (human melanoma) cells with IC50 of 44.3 ± 4.2 µg mL-1 (135 ± 13 µmol L-1) and 41.5 ± 7.5 µg mL-1 (126 ± 23 µmol L-1), respectively, similar to positive control cisplatin (IC50 = 43.2 ± 3.2 µg mL-1 or 144 ± 11 µmol L-1). Otherwise, compound 4 was inactive (IC50 > 100 µg mL-1 or > 300 µmol L-1). The obtained results provide important data for the selection of bioactive neolignans with promising cytotoxic potential using a simple and fast method employing a green solvent as 1-butyl-3-methylimidazolium bromide (BMImBr).