UJI AKTIVITAS ANTI KANKER SENYAWA TURUNAN ESTER α-MANGOSTIN MELALUI PENDEKATAN MOLECULAR DOCKING SECARA IN SILICO

AZMI ALWI, - (2025) UJI AKTIVITAS ANTI KANKER SENYAWA TURUNAN ESTER α-MANGOSTIN MELALUI PENDEKATAN MOLECULAR DOCKING SECARA IN SILICO. Skripsi thesis, Sekolah Tinggi Farmasi Indonesia.

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Abstract

Kanker merupakan penyebab kematian utama di dunia dan masih menjadi tantangan besar dalam terapi modern karena resistensi obat dan efek samping kemoterapi. Senyawa alami seperti α-mangostin dari kulit manggis memiliki potensi sebagai agen antikanker karena aktivitas biologis dan struktur kimianya yang dapat dimodifikasi. Penelitian ini bertujuan untuk mengevaluasi potensi aktivitas antikanker dari 3 senyawa turunan ester α-mangostin terhadap tiga target protein kanker, secara in silico menggunakan metode molecular docking pada Glutathione S-transferase P (3CSH), Estrogen Receptor Beta (1QKM), dan Epidermal Growth Factor Receptor (1XKK). Modifikasi struktur α-mangostin dilakukan melalui proses esterifikasi untuk meningkatkan afinitas, bioavailabilitas, dan efektivitas biologis. Preparasi dan validasi protein serta ligan dilakukan menggunakan perangkat lunak YASARA dan PLANTS. Parameter utama yang dianalisis meliputi nilai skor docking dan visualisasi interaksi molekuler. Turunan ester α-mangostin yang akan digunakan pada penelitian ini diantaranya adalah 1,6-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo-9H-xanthen-3-yl acetate (Turunan 1); 6-(acetyloxy)-1-hydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo-9Hxanthen-3-olate(Turunan2);6(acetyloxy)-1-hydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo-9Hxanthen-3-ylacetat (Turunan 3). Hasil menunjukkan bahwa Turunan 3 memiliki score docking lebih tinggi dari α-mangostin terhadap protein 3CSH, sedangkan Turunan 1 dan 2 menunjukkan aktivitas lebih tinggi terhadap target 1XKK. Mekanisme kerja Turunan 3 diperkirakan melalui inhibisi enzim GSTP yang berperan dalam detoksifikasi dan resistensi obat, sehingga dapat mengganggu jalur proliferasi sel kanker dan meningkatkan efektivitas kemoterapi. Sementara itu, Turunan 1 dan 2 berpotensi menghambat aktivitas tirosin kinase pada EGFR dengan cara berikatan kuat pada domain aktifnya, yang dapat menghambat jalur pensinyalan MAPK dan PI3K/AKT yang penting dalam proliferasi dan kelangsungan hidup sel kanker. Secara keseluruhan, turunan ester α-mangostin menunjukkan potensi lebih unggul dibandingkan senyawa induknya sebagai kandidat obat antikanker berbasis bahan alam. ---- Cancer is the leading cause of death worldwide and remains a major challenge in modern therapy due to drug resistance and the adverse side effects of chemotherapy. Natural compounds such as α-mangostin from mangosteen pericarp have shown potential as anticancer agents due to their biological activity and modifiable chemical structure. This study aims to evaluate the anticancer potential of three ester derivatives of α-mangostin against three cancer-related protein targets, in silico using the molecular docking method on Glutathione S-transferase P (3CSH), Estrogen Receptor Beta (1QKM), and Epidermal Growth Factor Receptor (1XKK. Structural modifications of α-mangostin were carried out via esterification to improve affinity, bioavailability, and biological effectiveness. Protein and ligand preparation and validation were performed using YASARA and PLANTS software. Key parameters analyzed included docking scores and molecular interaction visualizations.The α-mangostin ester derivatives used in this study were: 1,6-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo-9H-xanthen-3-ylacetate(Derivative1);6-(acetylo oxy)-1-hydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1-yl)-9-oxo9Hxanthen-3-olat e(Derivative2);and6-(acetyloxy)-1-hydroxy-7-methoxy-2,8-bis(3-methylbut-2-en-1 -yl)-9-oxo-9H-xanthen-3ylacetate(Derivative3). The results showed that Derivative 3 had higher activity than α-mangostin against the 3CSH protein, while Derivatives 1 and 2 showed higher activity against the 1XKK target. The mechanism of Derivative 3 is predicted to involve inhibition of the GSTP enzyme, which plays a role in detoxification and drug resistance, thereby potentially disrupting cancer cell proliferation pathways and enhancing chemotherapy effectiveness. Meanwhile, Derivatives 1 and 2 are likely to inhibit tyrosine kinase activity in EGFR by strongly binding to its active domain, which may block the MAPK and PI3K/AKT signaling pathways crucial for cancer cell proliferation and survival. Overall, α-mangostin ester derivatives exhibit greater potential than the parent compound as natural product-based anticancer drug candidates.

Item Type: Thesis (Skripsi)
Uncontrolled Keywords: α-mangostin, esterifikasi, kanker, molecular docking, in silico ----- α-mangostin, esterification, cancer, molecular docking, in silico
Subjects: Q Science > Q Science (General)
R Medicine > R Medicine (General)
Divisions: Program Studi S1 Farmasi
Depositing User: pustakawan - -
Date Deposited: 13 Aug 2025 03:44
Last Modified: 28 Aug 2025 01:59
URI: http://repository.stfi.ac.id/id/eprint/2696

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