CHEMICAL TRANSFORMATION OF XANTHORRHIZOL AND METABOLOMIC ANALYSIS OF TEMULAWAK RHIZOMES (CURCUMA XANTHORRHIZA) GROWN IN DIFFERENT MEDIA

• Main Author: Purnamasari, Yunita
• Format: Dissertations
• Language: Indonesia
• Subjects: Kimia
• Online Access: https://digilib.itb.ac.id/gdl/view/86734
• Institution: Institut Teknologi Bandung

Curcuma xanthorrhiza, often known as temulawak, is a native Indonesian medicinal plant that has been grown around the world. This growth has reportedly identified active components from the sesquiterpene and diarylheptanoid groups. Temulawak contains a particular chemical called xanthorrhizol (1), a member of the bisabolane sesquiterpene group, absent from other rhizome plants. Many bioactivities, including anticancer, antibacterial, anti-inflammatory, antioxidant, antihyperglycemic, antihypertensive, antiplatelet, nephroprotective, hepatoprotective, estrogenic, and anti-estrogenic actions, have been found in xanthorrhizol (1). The transformation of xanthorrhizol through various reactions can lead to the development of new compounds with potential applications in various fields. Xanthorrhizol (1) was changed in this study by adding a functional group containing a nitrogen atom. Xanthorrhizol (1) was first isolated from C. xanthorrhiza rhizomes for this investigation. The transformation xanthorrhizol (1) is carried out by a nitration reaction and substitution of the hydroxyl group with compounds containing nitrogen atoms, including morpholine, benzylamine and quinazoline, which are first reacted with 1-bromo-3-chloropropane under alkaline conditions. The structure of the transformed compound was determined based on FTIR, 1D-NMR (1H NMR and 13C-NMR) and 2D-NMR (HSQC and HMBC) spectroscopy data and mass spectroscopy. Compounds such as 2-nitroxanthorrhizol (2), 4-nitroxanthorrhizol (3), 2,4 dinitroxanthorrhizol (4), yl)phenoxy)propyl)morpholine 4-(3-(2-methyl-5-(6-methylhept-5-en (5), -2 N-benzyl-3-(2-methyl-5-(6-methylhept-5-en-2 yl)phenoxy)propan-1-amine (6), and 6,7-dimethoxy-3-(3-(2-methyl-5-(6-methylhept-5-en-2 yl)phenoxy)propyl)quinazolin-4(3H)-one (7) are the compounds produced by the six transformations of santorizol. By nitrating xanthorrhizol (1), compounds 2, 3, and 4 were created, yielding 32.8%, 27.5%, and 25.5% of the reaction. In the meantime, compounds 5, 6, and 7 were produced by substituting other compounds containing nitrogen atoms for the hydroxyl group of xanthorrhizol (1), yielding 15.0%, 8.8%, and 14.8% of the original product. Xanthorrhizol (1) and its six derivatives were evaluated against Bacillus subtilis, Streptococcus aureus, Salmonella typhi, and Pseudomonas aeruginosa to determine their inhibitory effect against the caspase-7 enzyme. In contrast to the standard, Z-VAD-FMK, which gives 100% inhibition, compounds 2 and 3 provide inhibition values of 16% and 11% in the enzyme activity test against caspase-7, respectively. These results fall into the weak group. Xanthorrhizol and its derivatives had low to high activity against the four tested bacteria, according to the results of the antibacterial activity test. Compound 3 exhibited the strongest action against two gram positive bacteria (B. subtilis and S. aureus) out of all the compounds examined. This study successfully evaluated the metabolite profile of C. xanthorrhiza rhizomes grown in different growing media and ages using 1H NMR-based metabolomics. Temulawak rhizomes are taken in the fourth to ninth month of growth and planted in a soil medium, namely soil: husk (2:1) and soil:husk: manure (1:1:1). Rhizome samples were extracted directly with deuterated solvents, namely D2O and CDCl3, which were then measured using NMR spectroscopy. Compounds in rhizome samples were identified by detecting characteristic signals in the 1H NMR spectrum and further specialized by 2D NMR spectrum analysis, including 1H-1H gCOSY, 1H-1H zTOCSY, and J-Resolved. A total of 17 primary metabolites and 23 secondary metabolites were found in C. xanthorrhiza rhizomes. C. xanthorrhiza rhizomes mass analysis, metabolite profiles, and multivariate data indicate that an ideal harvest age of eighty is reached. It yields the most extensive mass rhizomes and the maximum concentration of contributing components xanthorrhizol (1), 3,4-dihydroxybisabola-1,10-diene (22), acetic acid (71), succinic acid (73), and valine (78)) in the eighth month.