Anticancer and Antivirus Activities of two Biflavonoids from Indonesian Araucaria hunsteinii K Schum Leaves

Abstract

Araucaria genera consist of 19 species, and three of them are grown in Botanical Garden, Bogor, Indonesia. These plants were reported to contain biflavonoids and are primarily found in leaves. Biflavonoids display an extensive range of biological properties such as anti-inflammatory, anti-oxidant, anti-tumor, antivirus, anti-microbial, anti-fungal, etc. However, no studies reported secondary metabolites, especially biflavonoids, from Indonesian A. hunsteinii leaves. Therefore, this research aims to isolate biflavonoid from A. Hunsteinii leaves and evaluate their anticancer and antivirus activities. First, A. hunsteinii leaves were macerated in acetone to give brownish-black crude extract (14.66%, w/w). Then, the natural extract was fractionated and purified using chromatographic techniques with silica gel and Sephadex LH-20 as a stationary phase to afford two isolated compounds. The acetone extract and two isolated compounds were examined for their cytotoxic activity against breast cancer MCF-7 cells and human immunodeficiency virus (HIV) SRV-2 viruses based on an assay of 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). According to spectroscopic data, including IR, UV-Vis, LC-MS/MS, and NMR (1H, 13C, NOESY, HSQC, and HMBC), two compounds were successfully elucidated as 4',7,7''-tri-O-methylcupressuflavone (1) and 4''',7,7''-tri-O-methylagathisflavone (2). Both compounds were first isolated from A. hunsteinii leaves. The preliminary MTT assay of compounds 1 and 2 against MCF-7 cells showed IC50 of 91.74 and 314.44 µg/mL, respectively. They had a larger IC50 than an acetone extract of A. hunsteinii leaves (IC50 of 62.16 g/mL), indicating that all samples had lower activity than the positive control, epirubicin HCl (IC50 of 0.52 g/mL). Furthermore, both compounds were ineffective as antivirus agents against SRV-2 viruses.