Pasaribu, Yenni Pintauli (2022) Isolasi, Modifikasi Struktur, Dan Studi Bioaktivitas Senyawa Fenolat Serta Derivatnya Dari Tumbuhan Garcinia Sabangensis Lauterb.Dan Garcinia Celebica L. Endemik Papua Indonesia. Doctoral thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Kajian terhadap dua tumbuhan Garcinia (Fam. Clusiaceae) asal Papua yaitu Garcinia sabangensis Lauterb. dan Garcinia celebica L. dilakukan berdasarkan kajian etnobotani dan filogenetik dimana Garcinia adalah sumber senyawa fenolat yang unik, yaitu turunan santon, benzofenon, biflavon, bifenil, dan depsidon yang dilaporkan memiliki beragam bioaktivitas termasuk antimalaria dan antikanker. Modifikasi senyawa fenolat dengan glikosilasi dilakukan untuk menghasilkan derivat baru dan meningkatkan bioaktivitasnya. Penelitian ini bertujuan memperoleh senyawa-senyawa fenolat baru maupun yang sudah dilaporkan sebelumnya serta menyusun saran biosintesis senyawa-senyawa tersebut, mengkategorikan bioaktivitas antikanker dan antimalaria senyawa-senyawa dari kedua spesies, dan memperoleh senyawa fenolat termodifikasi. Bagian kulit akar G. celebica dan bagian kulit batang serta ranting G. sabangensis ditetapkan sebagai sampel pada penelitian ini. Prosedur isolasi senyawa fenolat yang dilakukan meliputi preparasi/penyiapan sampel, uji pendahuluan, ekstraksi menggunakan metode maserasi, fraksinasi menggunakan metode kolom kromatografi, pemurnian menggunakan metode kolom kromatografi, dan rekristalisasi, serta penentuan struktur senyawa menggunakan data dan spektrum MS, UV, IR, NMR 1 dan 2 dimensi (1H-NMR, 13C-NMR, DEPT 135, HSQC, COSY, HMBC). Prosedur modifikasi senyawa fenolat menggunakan metode glikosilasi. Aktivitas antikanker terhadap sel kanker serviks HeLa, sel kanker payudara MCF-7, sel kanker paru A549, dan sel kanker kulit B16 diuji menggunakan PrestoBlue (PB) Assay, sedangkan aktivitas antimalaria terhadap parasit P. falciparum strain 3D7 diuji menggunakan metode lactate dehydrogenase (LDH). Dari hasil penelitian ini diperoleh senyawa fenolat golongan benzofenon poliprenilasi (polyprenylated benzophenones, PPB) yaitu (-)-siklosantosimol (1), isosantosimol (2), dan santosimol (3) dari G. celebica dan 7-epigarcinol (4) dari G. sabangensis. Modifikasi santosimol (3) menghasilkan senyawa 19-iodosantosimol (5). Pengujian bioaktivitas antikanker terhadap senyawa (1-3) menunjukkan bahwa ketiga senyawa tersebut memiliki sifat antikanker yang baik, senyawa (2) memiliki aktivitas antikanker terbaik terhadap tiga sel kanker yang diujikan, yaitu sel kanker HeLa (IC50 10.18 μM), MCF-7 (IC50 10.73 μM), dan B16 (IC50 12.39 μM), sedangkan senyawa (1) menunjukkan aktivitas terbaik terhadap sel kanker A549 (IC50 13.77 μM) dibandingkan dengan kontrol positif cisplatin (IC50 HeLa 19 μM, IC50 MCF7 53 μM, IC50 A549 18 μM, dan IC50 B16 43 μM). Pengujian bioaktivitas antiplasmodial menunjukkan bahwa senyawa (2) memiliki aktivitas antiplasmodial terhadap parasit malaria P. falciparum strain 3D7 dibandingkan senyawa-senyawa lainnya dengan persen penghambatan 83,97% pada konsentrasi 10 μg/mL dan IC¬50 2,99 μM dengan kontrol positif klorokuin dengan persen penghambatan 98,8% dan IC50 0,006 μM.
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The study on two species of Garcinia (fam. Clusiaceae), namely Garcinia sabangensis Lauterb. and Garcinia celebica L., was conducted based on ethnobotanical and phylogenetic studies that Garcinia is a source of unique phenolic compounds, including xanthones, benzophenones, biflavones, biphenyls, and depsidones, which are reported to have various bioactivities including antimalarial and anticancer. Modification of phenolic compounds by glycosylation was carried out to produce new derivatives and increase their bioactivity. This research aimed to obtain novel and known phenolic compounds and to propose biogenesis pathway for the two species, to categorize the antimalarial and anticancer bioactivities of isolated xanthones derived from the two species, and to obtain modified phenolic compound through glycosylation. The root bark of G. celebica and the stem barks and branches of G. sabangensis were selected as samples in this study. Isolation procedure of phenolic compounds consist of preparation of sample, preliminary tests, extraction using the maceration method, fractionation using the column chromatography method, purification using the column chromatography and recrystallization methods, determining the structure of the compound using data and spectra of MS, UV, IR, NMR 1 and 2 dimensions (1H-NMR, 13C-NMR, DEPT-135, HSQC, COSY, and HMBC). Modification procedure of phenolic compound using glycosylation method. The in vitro cytotoxic assay against the HeLa (human cervix adenocarcinoma), MCF-7 (human breast adenocarcinoma), A549 (human lung carcinoma), and B16 (murine melanoma) cancer cell lines was performed using the PrestoBlue (PB) Assay, while the in vitro antiplasmodial assay against P. falciparum strain 3D7 was performed using the lactate dehydrogenase (LDH) method. A total of four polyprenylated benzophenones: (-)-cycloxanthochymol (1), isoxanthochymol (2), dan xanthochymol (3) were obtained from the root barks of G. celebica and 7-epigarcinol was obtained from the mixture of stem barks and twigs of G. sabangensis, while 19-iodoxanthochymol (5) was obtained from the modification of xanthochymol. Anticancer bioactivity evaluation of compounds (1)-(3) showed that the three compounds exhibited adequate cytotoxicity, which isoxanthochymol (2) had the best cytotoxicity against the three tested cancer cell lines, HeLa (IC50 10.18 μM), MCF- 7 (IC50 10.73 μM), and B16 (IC50 12.39 μM), while (-)-cycloxanthochymol (1) showed the best activity against cancer cells A549 (IC50 13.77 μM) compared to cisplatin positive control (IC50 HeLa 19 μM, IC50 MCF7 53 μM, IC50 A549 18 μM, and IC50 B16 43 μM). Antiplasmodial bioactivity assay exhibited that isoxanthochymol (2) was active against P. falciparum strain 3D7 with an inhibition percentage of 83.97 at 10 μg/mL (IC50 2.99 μM).
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Garcinia celebica, Garcinia sabangensis, polyprenylated benzophenone, antimalaria, antikanker. |
| Subjects: | Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry Q Science > QD Chemistry > QD471 Chemical compounds - Structure and formulas |
| Divisions: | Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47001-(S3) PhD Thesis |
| Depositing User: | YENNI PINTAULI PASARIBU |
| Date Deposited: | 26 Jan 2023 04:02 |
| Last Modified: | 26 Jan 2023 04:02 |
| URI: | http://repository.its.ac.id/id/eprint/95651 |
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