Studi Potensi Senyawa Aktif Bayam Merah (Amaranthus gangeticus) sebagai Inhibitor CHK1 dan PARP secara In Silico

Abstract

Background: Breast cancer was the uncontrolled growth of abnormal cells in breast tissue. Treatment of breast cancer with CHK1 and PARP inhibition caused damage in all cell lines, triggering apoptosis. The use of red spinach as a naturalbased treatment was still not optimal, so in silico testing was needed. Objective: This study aimed to predict the potential of active compounds from red spinach to inhibit CHK1 and PARP receptors and to meet pharmacokinetic parameters as potential anti-cancer compounds in silico. Methods: The study was conducted by validating the method using PyMOL, performing molecular docking with Autodock Vina, and predicting pharmacokinetics such as Human Intestinal Absorption (HIA), Volume Distribution Steady State (VDSS), Fraction Unbound, CYP substrate and inhibitor, and total clearance using the pkCSM website for CHK1 and PARP receptors. Results: The results showed that the docking validation values for CHK1 and PARP receptors were 1.5 Å and 1.088 Å. The docking simulation results identified amino acid residues LEU 15, VAL 23, LEU 137, and SER 147 as binding pockets for the CHK1 receptor, while amino acid residues TYR 907, SER 904, and GLY 863 were identified as binding pockets for the PARP receptor. The study revealed that 13 red spinach compounds met the specified pharmacokinetic parameters. The compound 3-(3,4-Dihydroxycinnamoyl) quinic acid was predicted to have inhibitory activity against CHK1 and PARP and to meet pharmacokinetic activity requirements, suggesting its potential in treating breast cancer in silico. Conclusion: This study found that the active compounds of red spinach were predicted to be utilized as inhibitors of CHK1 and PARP receptors.