Studi Komputasi Hubungan Aktivitas Senyawa Turunan Asam Galat sebagai Inhibitor Reseptor Androgen pada Kanker Prostat

Abstract

Abstract
Gallic acid is a secondary metabolite compound found in several natural products and has several cytotoxic activities against some cell lines such as breast, colon, prostate, and cervical cancer. This research was aimed to study the stability, affinity, and interaction of gallic acid compounds and their derivatives as well as comparative ligand against androgen receptor through a computational approach, namely in silico molecular docking. The research was conducted in four stages, namely the preparation and optimization of ligand compounds and androgen receptor macromolecules, docking simulation process, and analysis and visualization of simulation results. Computational studies show that gallic acid derivatives provide better inhibitory activity than gallic acid and comparative ligand with an average ΔG value of -7,34 kcal/mol. Compound 3,4,5 tri-methoxy-phenyl-ethyl gallate had the best binding energy value of 8.20 kcal/mol. This was demonstrated by stability, affinity, and strong interactions towards active site amino acids at the androgen receptor. Besides, the formed hydrogen bond was strong enough with an average distance of <3.5 Ǻ which might lead to inhibition and apoptosis through activation of caspase 3 and 9 in prostate cancer cells. Thus, gallic acid derivatives have the potential as inhibitors of androgen receptors and become candidates for new drugs in prostate cancer.
Keywords: computational studies, molecular docking, gallic acid and its derivatives, androgen receptor, prostate cancer

Abstrak
Asam galat merupakan senyawa metabolit sekunder yang ditemukan pada beberapa produk alami dan memiliki beberapa aktivitas sitotoksik terhadap beberapa sel line seperti kanker payudara, kolon, prostat, dan serviks. Penelitian ini bertujuan mempelajari stabilitas, afinitas, dan interaksi senyawa asam galat dan turunannya, serta ligan pembanding terhadap reseptor androgen melalui pendekatan secara komputasi yaitu in silico molekuler docking. Penelitian dilakukan dengan empat tahapan yaitu preparasi dan optimasi senyawa ligan, serta makromolekul reseptor androgen, proses simulasi docking dan analisis, serta visualisasi hasil simulasi. Studi komputasi menunjukkan bahwa senyawa turunan asam galat memberikan aktivitas inhibisi yang lebih baik dibandingkan asam galat dan ligan pembanding dengan rata-rata nilai ΔG sebesar -7,34 kkal/mol. Senyawa 3,4,5 trimetoksi-feniletil galat memiliki nilai binding energy terbaik sebesar -8,20 kkal/mol. Hal ini ditunjukkan dengan stabilitas, afinitas, dan interaksi yang kuat terhadap situs aktif asam amino pada reseptor androgen. Selain itu, terbentuk ikatan hidrogen cukup kuat dengan rata-rata jarak

Kata kunci: studi komputasi, molekular docking, asam galat dan turunannya, reseptor androgen, kanker prostat