SECONDARY METABOLITES FROM INDONESIAN CRYPTOCARYA AND THEIR POTENCY AS ANTICANCER

• Main Author: Nabila Farahnita, Shaffa
• Format: Final Project
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/69054
• Institution: Institut Teknologi Bandung

Leukemia (blood cancer) is a type of cancer which is one of the most leading cause of death and has a poor case history m the world . One of the treatments to manage leukemia is conducted by targeting apoptotic pathways, specifically by targeting the protein receptors which regulat its pathway, including Bcl-2 and Bcl-xL proteins. Up to now, commercial inhibitors which are used to inhibit the proteins are venetoclax and navitoclax. However, both inhibitors are still causing side effects for the patients, such as drug resistance. Therefore, it is necessary to look for an alternative drug source, based on natural products, such as from plants. Indonesian plants that has been reported to have anticancer activity are plants from Cryptocarya genus. This is proven by their significant anticancer activity against murine leukemia murine P-388 cells by in-vitro testing, such as cryptocaryone (C. konishii) and goniothalamin (C. massoia). Therefore, it can be studied further by seeking their natural secondary metabolites, particularly by isolating secondary metabolites of Cryptocarya Indonesia plants and verify the potency as anticancer inhibitor specifically by in silica method , like molecular docking. In this research, isolation of secondary metabolites of Cryptocarya Indonesia, particulary Cryptocarya massoi, has been carried out. In addition, to the potency study of the inhibition ability towards Bcl-2 and Bcl-xL of the isolated compounds from Cryp tocarya massoia and flavonoids derivatives from Cryptocarya konishii by using molecular docking has also been conducted. Isolation of secondary metabolites of Cryptocarya massoia bark was carried out in several steps, including maceration of bark powder with acetone solvent, fractionation of acetone extract and purification of the obtained fractions using various chromatographic techniques such as Vacuum Liquid Chromatography (VLC) and Gravity Column Chromatography (GCC), and characterized the structure of the isolated compounds by NMR spectroscopy. Determination of the structure of the isolated compound was carried out based on ID-NMR (+H-NMR and 13C-NMR) and 2D-NMR (HSQC and HMBC) spectroscopic data showed that two known compounds has been obtained from stem bark of Cryptocarya massoia, identified as stigmast-4-en-3-one as the steroid derivatives that found for the first time from Cryptocarya massoia but has been isolated from Ctyptocarya idenburgensis, and C-10 massoialactone as the main compound from Cryptocarya massoia. Moreover, the result of molecular docking showed that kurzichalcolactone from C. konishii has the best inhibition potential towards Bcl-2 and Bcl-xL, with their docking score sequentially , -9,7 kcal/mol and -11 kcal/mo!. Hydrophobic interactions between Bcl-2 and Bcl-xL hot spot residues play important role in the inhibition mechanism of kurzichalcolactone . As a result, this compound has the potency to be developed further as an anticancer agent.