#TITLE_ALTERNATIVE#

• Main Author: RIZKI ALDILLA (NIM : 20513029) ; Pembimbing Dr. Lia Dewi Juliawaty, VINA
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/19625
• Institution: Institut Teknologi Bandung

Agathis is one of the major genus in Araucariaceae family, besides Araucaria and Wollemia. Agathis is a city greenery plant. Its wood has been known to have high quality. Therefore, it is usually used for some industrial purposes, such as building material, furniture, and paper production. In Indonesia, Agathis can be found in tropical rain forests area, in Kalimantan and Sumatra. Biflavonoid is a major secondary metabolite found in Agathis, along with norlignans and diterpenoids. Biflavonoid, known as flavon dimmers, composed from two monomer units of flavonoid through oxidative coupling reaction. Biflavonoids in Agathis usually formed from two apigenin units. They have distinctive skeleton structure and they are known to have anticancer activity against variety of cancer cells, such as NCI-H460 (lung), MCF-7 (breast), Ovcar-9 (ovarian), and P-388 (leukemia) cells. Beside that, biflavonoid derivatives were also reported to have significant activities, such as antimalarial, anti-HIV, antiinfluenza, antiepileptic, and as BACE-1 enzyme inhibitors for Alzheimer 's. One of Agathis species growing in Indonesia is A. borneensis, locally known as „dammar pilau„. A. borneensis leaves are commonly used as traditional medicine to heal wounds by local people in Kalimantan. Up to now, the chemical studies on biflavonoids in A. borneensis and their cytotoxic activity against murine leukemia P-388 cells has not been reported yet. Therefore, this research have been conducted to isolate biflavonoids from A. borneensis and to examine their cytotoxic activity against murine leukemia P-388 cells. The isolation of biflavonoid has been conducted using various of chromatographic techniques, such as vacuum liquid chromatography (VLC), gravity column chromatography (GCC) with silica and Sephadex LH - 20 as stationary phases. Five biflavonoid derivatives have been obtained from A. borneensis leaves and identified as 4',4"',7,7'-tetra-O-methylamentoflavon, 4',4"',7-tri-O-methylcupressuflavon, 7,4' or 4"'-di-O-methylcupressuflavon, 7-mono-O-methylcupressuflavon, and cupressuflavon based on spectroscopic data including NMR spectroscopy ( 1H, 13C , HSQC , HMBC, and NOESY ), IR spectroscopy, UV - Vis spectroscopy and Mass spectroscopy. Two compounds, namely 7,4' or 4"'-di-O-methylcupresuflavon and 4',4"',7-tri-O-methylcupresuflavon were reported for the first time from Agathis. The preliminary assay of acetone extract of A. borneensis leaves showed active result against murine leukemia P-388 cells with IC50 4.24 μg/mL. This assay was preliminary assay in screening of cytotoxic activity suggested by NCI (National Cancer Institute). Moreover, the five isolated compounds were also examined for their cytotoxic activities. Two compounds, i.e. 7-mono-O-methylcupressuflavon and cupressuflavon, were very active result with IC50 1.26 μg/mL and 0.87 μg/mL, respectively. One compound, i.e. 7,4' or 4"'-di-O-methylcupressuflavon, was active with IC50 3.59 μg/mL. Therefore, the three compounds are potential to be the lead compounds for anticancer. Structure and activity relationships between cupressuflavon and its methylether derivatives were also analyzed. Based on differrent substituents on each compounds, it can be sugessted that methylation on phenolic group at A or B ring can decrease the activity against murine leukemia P-388 cells.