ISOLATION AND TRANSFORMATION OF SECONDARY METABOLITE FROM PERICARP OF GARCINIA MANGOSTANA AND BIOACTIVITY AS TYROSINE KINASE INHIBITOR

• Main Author: SUHADA, AKMEL
• Format: Theses
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/63783
• Institution: Institut Teknologi Bandung

Garcinia mangostana, known by the Indonesian people as mangosteen, is a fruit plant originated from East India, the Malay Peninsula, and Southeast Asia, including Indonesia. G. mangostana is natural sources of xanthone-derived compounds, especially in the pericarp of the fruit which is reported to contain rich of prenylated xanthones. This group of compounds from this plant has been reported for its biological properties, such as antibacterial, antioxidant, anti-inflammatory, anticancer, antiobesity, ?-amylase inhibitor, and anticancer. The diversity of bioactivity possessed by these xanthone derivatives has been raised interest in conduct for research and potential exploration of secondary metabolites from the plant G. mangostana. One of the derivatives of trepenylated xanthones, namely -mangostin, is the main compound found in G. mangostana and has been widely reported by previous studies. This has become an advantage that is widely used by researchers by making - mangostin compounds as one of the objects in various biological properties tests, modifications and transformations. In this study, the isolation of secondary metabolites from the rind of G. mangostana, transformation of isolated compounds, characterization of the structure of isolated and transformed compounds, and determination of biological properties as tyrosine kinase receptor inhibitors were carried out in this study. Isolation of secondary metabolites from the rind of G. mangostana involved several stages, among others, extraction of the pericarp of G. mangostana (maceration) with acetone solvent to obtain acetone extract, fractionation, and purification using vacuum liquid chromatography (KCV) and radial chromatography (KR) methods. . The transformation was carried out on the secondary metabolites isolated with 1-bromo-3-chloropropane and morpholine. The molecular structures of isolated and transformed compounds were determined based on spectroscopic data of 1D-NMR (1H-NMR and 13C-NMR) and 2D-NMR (HSQC and HMBC). Determination of biological properties as tyrosine kinase receptor inhibitors from isolated compounds and transformed compounds was evaluated against eight receptor tyrosine kinase enzymes, including HER1/EGFR, HER2, HER4, PDGFR-?, PDGFR-?, IGFR1R InsR, and KDR using the ADP-GloTM method. Tyrosine kinase receptor is part of the tyrosine kinase enzyme that plays an important role in cell regulation so that it becomes a target in curing cancer or anticancer diseases. A total of three pure compounds derived from prenylated xanthones were isolated and identified from the fruit skin of G. mangostana, namely -mangostin (1), -mangostin (3) and 3-isomangostin (29). The compound -mangostin (1) is the main compound of G. mangostana as previously reported. The result of the transformation of the isolated compound -mangostin (3) with 1-bromo-3-chloropropane which was reacted for 24 hours at 60? in acetone solvent, produced two pure compounds which were successfully separated as BC1 and BC2. The yield of each compound obtained was 33% (BC1) and 10% (BC2). Then, the transformation of the isolated compound - mangostin (1) with 4-(3-chloropropyl)morpholine and 1-bromo-3-chloropropane for 24 hours at 80? in acetonitrile solvent obtained five pure compounds which were successfully separated as ABM1, ABM3, ABM5, ABM8, and ABM10. The yields of each of the five transformed compounds were 10% (ABM1), 15% (ABM3), 10% (ABM5), 10% (ABM8) and 8% (ABM10). The results of the tyrosine kinase receptor inhibition bioactivity test showed that -mangostin (1) and -mangostin (3) compounds were classified as weak receptor tyrosine kinase inhibitors with the respective bioactivity of -mangostin (1) against HER2 by 23% and -mangostin (3) to EFGR by 11% and HER2 by 30%. Meanwhile, the transformed compounds ABM5, ABM8 and ABM10 showed inhibitory activity against tyrosine kinase receptors which were classified as inactive.