Studi In Silico Fitosterol dan Turunannya Sebagai Obat Anti Kanker Payudara

In-Silico Phytosterol Study and Its Derivatives as Anti-Breast Cancer Drugs

Fitosterol berpotensi dalam menghambat pertumbuhan kanker payudara, salah satunya β-Sitosterol yang dibuktikan pengurangan ukuran tumor setelah konsumsi pada studi sebelumnya. Penelitian ini bertujuan mengkaji kandidat obat anti kanker payudara dari senyawa fitosterol dan turunannya. Studi in silico dilakukan dengan metode Hubungan Kuantitatif Struktur dan Aktivitas (HKSA) dan diperkuat dengan metode penambatan molekular. Deskriptor HKSA yang digunakan adalah elektronik, sterik dan hidrofobik. Karakter dari masing-masing deskriptor dikomputasikan menggunakan NWchem dan Gamess (metode DFT, basis set 6-31*), SwissAdme, Molinspiration, dan pkCSM. Penambatan dan visualisasi molekul dilakukan dengan Autodock Tools 1.5.6 dan Biovia Discovery Studio 2019. Hasilnya menunjukkan bahwa model persamaan terbaik HKSA senyawa bahan obat dari turunan senyawa fitosterol adalah Log P = 316.46 + (-1.513×MR) + (-0.668×V) + (3.926×P) + (-18.235×Homo) + (2.757×Lumo), dari persamaan tersebut diperoleh senyawa terbaik 

Phytosterols and their derivatives have the potential to inhibit the growth of breast cancer, one of which is β-sitosterol, which has been shown to reduce tumor size after consumption in previous studies. This study aims to examine anti-breast cancer drugs from phytosterol compounds and their derivatives. The study was conducted using the Quantitaitve Structur-Activity Relationship method and strengthened by the molecular docking method. The QSAR descriptor used was electronic, steric and hydrophobic. The characters of each descriptor were computed using NWchem and Gamess (DFT method, 6-31 * base set), SwissAdme, Molinspiration, and pkCSM. Tethering and molecular visualization were carried out with Autodock Tools 1.5.6 and Biovia Discovery Studio 2019. The results show that the best model of the HKSA equation for medicinal compounds from phytosterol compounds is Log P = 316.46 + (-1.513 * MR) + (-0.668 * V) + (3,926 * P) + (-18,235 * Homo) + (2,757 * Lumo), from this equation we get the best compound (9aR, 11aR) ‐7 ‐ chloro ‐ 1 - ((5R) ‐5‐ethyl‐6‐methylheptan‐2‐yl]‐9a,11a‐dimethyl‐1H, 2H, 3H, 3aH, 3bH, 4H, 6H, 7H, 8H, 9H, 9aH, 9bH, 10H, 11H, 11aH‐cyclopenta[a]phenanthren7‐ol. This compound was confirmed to have anti-cancer capabilities based on molecular docking with a target protein of 2W3L because it has a binding energy of -5.72 kcal / mol and an inhibition constant of 64.07 nM (nanomolar).