BIFLAVONOID DARI AGATHIS DAMMARA (ARAUCARIACEAE) SEBAGAI SENYAWA MODEL UNTUK ANTI ALZHEIMER’S

• Main Author: Waliana, Irpan
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/34935
• Institution: Institut Teknologi Bandung

Biflavonoids are kind of phenolic compounds which commonly occur in some conifers and ferns. Several genera that are known to contain bioflavonoid are Agathis, Cupressus, Podocarpus, Rhus, and Selaginella. Biflavonoid comprises of two flavonoid monomers, such as apigenin or naringenin, via oxidative coupling reaction. The oxidative coupling between two apigenin monomers generate some types of biflavonoid skeletons, namely cupressuflavone (A), agathisflavone (B), amentoflavone (C), robustaflavone (D), and hinokiflavone (E) that have differences on the linkage between monomers, either C-C or C-O-C. The secondary reactions on biflavonoids could happen, for example methylation, to produce methyl ether derivatives of biflavonoids. These secondary metabolites have characteristic structures and they also demonstrate several bioactivities, such as anti-cancer, anti-HIV, anti-epilepsy, and inhibitor of beta secretase (BACE-1) enzyme. Inhibitory activity of BACE-1 enzyme has a relation with inhibition of beta secretase enzyme activity in amyloid plaques formation. Up to now, amyloid plaques are the most discussed hypothesis as one of the causes of Alzheimer’s disease. Therefore, secondary metabolites having activity as inhibitor of BACE-1 enzyme have a great chance to be applied as lead compounds for anti Alzheimer’s. As Indonesia is a tropical country with a lot of diversity, it has a very big chance to investigate biflavonoids from its natural resources for pharmacological field, especially as inhibitor of BACE-1 enzyme. One of Indonesian’s plants known to contain biflavonoids is a kind of conifer of Agathis genus. This genus belongs to Aracauriaceae family which is a native plant from Southern hemisphere, such as Australia, New Zealand, and New Caledonia. By the time, this plant then also grows in Indomalaya and Asia Pacific. In Araucariaceae family, Agathis is a big genus with twenty one species and it is usually found as evergreen trees. There are approximately five Agathis species growing in Indonesia. Previous researches conducted on a number of Agathis species have reported that the major constituents of Agathis are flavonoids (biflavone), terpenoids (diterpene), and lignans (norlignan). One of Agathis species growing in Indonesia is Agathis dammara which commonly known as “dammar tree”. Dammar tree is a species which has high economical values because its timber and resin are used for industrial purposes, such as for paper, furniture, and varnish. Moreover, dammar tree has also an ecological value, especially for plantation tree. However, the phytochemical and pharmacological research on this species has never been conducted yet. In this research, twenty four of pure compounds have been isolated from leaves and twigs of A. dammara and they are identified as fifteen biflavonoids compounds belongs to cupressuflavone (A), agathisflavone (B), amentoflavone (C), robustaflavone (D), and hinokiflavone (E) skeletons. All of those compounds have been characterized using spectroscopic data, including UV-vis, MS, 1H-NMR, and 13C-NMR. Biflavonoids of amentoflavone (C), robustaflavone (D), dan hinokiflavone (E) skeletons are rare type of biflavonoids in Agathis species. Furthermore, thirteen compounds have been examined on their activity as BACE-1 enzyme inhibitor which play role in Alzheimer’s disease. This assay is also the first time reported for agathisflavone (B) skeleton type. Seven of those showed potential activity. Five compounds, namely as 7,7’’-di-O-methylcupressuflavone (10), 4’,7,7’’-tri- O-methylcupressuflavone (11), 7-O-methylagathisflavone (13), 4’’’,7-di-O- methylagathisflavone (14), 7,7’’-di-O-methylagatisflavone (15) are very active (IC50 = 0-2 µ M), with IC50 values of 0.44; 0.86; 0.66; 0.86; and 0.57 µ M, respectively. Two compounds known as bilobetin (18) and isoginkgetin (19) are active (IC50 = 2-10 µ M) with IC50 values of 2.02 and 3.01 µ M respectively. Meanwhile, the rest are not active. Finally, the finding of biflavonoids from Agathis dammara which have potent activity has a big chance to be applied as lead compounds for anti Alzheimer’s.