Rifaldi, Rifaldi (2023) Isolasi Senyawa Fenolat dari Ekstrak Metanol Kulit Batang Garcinia bancana Miq. dan Garcinia macrantha A.C.Sm. serta Aktivitasnya sebagai Antikanker dan Antimalaria secara In Silico dan In Vitro. Doctoral thesis, Institut Teknologi Sepuluh Nopember.
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Abstract
Garcinia bancana Miq. merupakan tumbuhan yang berasal dari hutan gambut Kalimantan Tengah, sedangkan Garcinia macrantha A.C.Sm. diketahui merupakan spesies endemik hutan kering Indonesia Timur asal pulau Halmahera Maluku Utara. Kedua spesies ini dipilih berdasarkan kajian filogenetik, dimana penelusuran literatur menunjukkan bahwa Garcinia merupakan genus sumber senyawa fenolat, khususnya santon dengan berbagai macam bioaktivitas termasuk antikanker dan antimalaria. Isolasi senyawa fenolat dari G. bancana Miq dan G. macrantha A.C.Sm. relatif belum banyak dilaporkan termasuk bioaktivitasnya sebagai antikanker dan antimalaria. Penelitian ini bertujuan mendapatkan data profil ekstrak kedua spesies untuk eksplorasi senyawa fenolat aktif, mendapatkan senyawa-senyawa fenolat baru dan yang telah diketahui beserta saran biogenesisnya dan mengklasifikasikan bioaktivitas antikanker dan antimalaria senyawa-senyawa dari kedua spesies. Bagian kulit batang kedua spesies ditetapkan sebagai sampel pada penelitian ini. Dalam penelitian ini, eksplorasi senyawa fenolat dilakukan melalui uji pendahuluan, uji kandungan fenolat total, uji kandungan flavonoid total, uji antioksidan ekstrak (DPPH, ABTS, dan FRAP), uji antimalaria ekstrak menggunakan metode pewarnaan giemsa, proses maserasi, fraksinasi menggunakan metode kolom kromatografi, pemurnian menggunakan metode kolom kromatografi dan rekristalisasi, dan elusidasi struktur mengunakan metoda spektroskopi UV-Vis, IR, HRESIMS, NMR 1 dan 2 dimensi (1H NMR, 13C NMR, HSQC, COSY, dan HMBC). Studi bioaktivitas secara in silico dilakukan terhadap enzim P. falciparum laktat dehidrogenase (PDB ID: 1CET) untuk antimalaria dan reseptor faktor pertumbuhan endotel vaskular 2 (VEGFR2) untuk antikanker. Selanjutnya, studi bioaktivitas secara in vitro antimalaria terhadap parasit P. falciparum galur 3D7 diuji menggunakan metode lactate dehydrogenase (LDH) sedangkan untuk antikanker dilakukan terhadap sel kanker Hela, MCF-7, A549, dan B16 menggunakan PrestoBlue Assay. Satu senyawa baru golongan bifenil yaitu macrabifenil A (5) telah berhasil diisolasi dari G. macrantha. Disamping itu juga telah berhasil diisolasi empat buah senyawa fenolat yang telah diketahui sebelumnya, antara lain: tiga senyawa golongan santon berupa macluraxanthone (1), isojacareubin (2), dan gerontoxanthone C 3 (3) dan satu senyawa golongan benzofenon poliprenilasi yaitu isogarcinol (4) dari G. bancana. Pengujian bioaktivitas antimalaria dan antikanker secara in silico menunjukkan bahwa senyawa (1-3) menghasilkan skor Moldock yang sebanding dengan obat komersial disertai ikatan hidrogen dan interaksi sterik dengan protein PfLDH/VEGFR2. Selanjutnya, pengujian bioaktivitas antimalaria senyawa (1-3) secara in vitro menunjukkan bahwa ketiga senyawa bersifat aktif dengan aktivitas terbaik ditunjukkan oleh senyawa (1) dengan kombinasi cincin dimetilpiran linear dan gugus dimetilalil dengan nilai IC50 sebesar 4,28±0,10 μM dibandingkan senyawa (3) (IC50 5,52±0,10 μM) yang mengandung cincin trimetilfuran angular dan gugus prenil dan senyawa (2) (IC50 11,45±0,30 μM) dengan struktur cincin dimetilpiran angular tanpa adanya substituen prenil. Pengujian bioaktivitas antikanker terhadap senyawa (1-3) menunjukkan bahwa ketiga senyawa bersifat moderat terhadap sel kanker dengan nilai IC50 masing-masing yaitu 8,45±0,03, 31,31±0,52, dan 9,69±0,02 μM untuk sel kanker A549; 12,99±0,43, 27,87±0,07, dan 14,86±0,27 μM untuk sel kanker MCF-7; 16,71±0,09, 31,10±0,26, 14,81±0,25 untuk sel kanker Hela; 12,20±0,02, 25,46±0,17, dan 13,52±0,31 μM untuk sel kanker B16. Namun, senyawa (1) dan (3) menunjukkan aktivitas yang kuat terhadap sel kanker A549 dengan nilai IC50 masing-masing 8,45±0,03 dan 9,69±0,02 μM dibandingkan kontrol positif cisplatin dengan nilai IC50 sebesar 18,00±0,01 μM.
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Garcinia bancana Miq. is a plant originated from the peat forest of Central Kalimantan, while Garcinia macrantha A.C.Sm is endemic to the dry forest of East Indonesia from Halmahera Island, North Maluku. These two species were selected based on phylogenetic studies, where a literature search showed that Garcinia is a genus of phenolic compounds, especially xanthones, with various bioactivities, including anticancer and antimalarial. Isolation of phenolic compounds from G. bancana Miq and G. macrantha A.C.Sm. relatively little reported, including its bioactivity as an anticancer and antimalarial. This study aims to obtain extract profile data of the two species for exploration of active phenolic compounds, obtain new and known phenolic compounds along with suggestions for their biogenesis and classify the anticancer and antimalarial bioactivity of the compounds of the two species. The bark of both species was determined as the sample in this study. In this study, exploration of phenolic compounds was carried out through preliminary tests, total phenolic and flavonoid content assay, antioxidant assay of extracts (DPPH, ABTS, and FRAP), antimalarial assay of extracts using giemsa staining method, maceration process, fractionation using column chromatography method, purification using column chromatography and recrystallization methods, and structure elucidation using UV-Vis, IR, HRESIMS, 1 and 2 dimensional NMR (1H NMR, 13C NMR, HSQC, COSY, and HMBC) spectroscopic methods. In silico bioactivity studies were carried out on the enzyme P. falciparum lactate dehydrogenase (PDB ID: 1CET) for antimalarial and vascular endothelial growth factor receptor 2 (VEGFR2) for anticancer. Furthermore, antimalarial in vitro bioactivity studies were carried out against the parasite P. falciparum strain 3D7 were tested using the lactate dehydrogenase (LDH) method, while anticancer were carried out on Hela, MCF-7, A549, and B16 cancer cells using the PrestoBlue Assay. A new compound of the biphenyl group, macrabphenyl A (5) has been successfully isolated from G. macrantha. In addition, four previously known phenolic compounds have been isolated, including: three xanthones group compounds, macluraxanthone (1), isojacareubin (2), and gerontoxanthone C 3 (3) and one polyprenylated benzophenone group compound, isogarcinol (4) from
G. bancana. In silico antimalarial and anticancer bioactivity tests showed that compounds (1-3) produced a Moldock score comparable to commercial drugs accompanied by hydrogen bonding and steric interaction with the PfLDH/VEGFR2 protein. Furthermore, in vitro antimalarial bioactivity evaluation of compounds (1-3) showed that the three compounds were active with the best activity exhibited by compound (1) with a combination of a linear dimethylpyran ring and a dimethylallyl group with an IC50 value of 4.28±0.10 μM compared to compound (3) (IC50 5.52±0.10 μM) containing an angular trimethylfuran ring and prenyl groups and compound (2) (IC50 11.45±0.30 μM) with an angular dimethylpyran ring structure without any prenyl substituents. Anticancer bioactivity assay of compounds (1-3) showed that the three compounds were moderate against cancer cells with respective IC50 values of 8.45±0.03, 31.31±0.52, and 9.69±0.02 μM for A549 cancer cells; 12.99±0.43, 27.87±0.07, and 14.86±0.27 μM for MCF-7 cancer cells; 16.71±0.09, 31.10±0.26, 14.81±0.25 for Hela cancer cells; 12.20±0.02, 25.46±0.17 and 13.52±0.31 μM for B16 cancer cells. However, compounds (1) and (3) showed potent activity against A549 cancer cells with IC50 values of 8.45±0.03 and 9.69±0.02 μM, respectively, compared to cisplatin positive controls with IC50 values of 18,00±0.01 μM.
| Item Type: | Thesis (Doctoral) |
|---|---|
| Uncontrolled Keywords: | Garcinia bancana, Garcinia macrantha, santon, benzofenon poliprenilasi, bifenil, antimalaria, antikanker ======================================================= Garcinia bancana, Garcinia macrantha, xanthones, polyprenylated benzophenone, biphenyl, antimalarial, anticancer |
| Subjects: | Q Science > QD Chemistry > QD251.2 Chemistry, Organic. Biochemistry Q Science > QD Chemistry > QD471 Chemical compounds - Structure and formulas Q Science > QD Chemistry > QD481 Chemical structure. |
| Divisions: | Faculty of Science and Data Analytics (SCIENTICS) > Chemistry > 47001-(S3) PhD Thesis |
| Depositing User: | Rifaldi Rifaldi |
| Date Deposited: | 28 Jul 2023 02:47 |
| Last Modified: | 28 Jul 2023 02:47 |
| URI: | http://repository.its.ac.id/id/eprint/100206 |
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