Analisis in Silico Potensi Penghambatan Protein WEE1 dan PLK1 dari Senyawa Aktif Bayam Merah (Amaranthus Gangeticus) pada Terapi Kanker Payudara

Abstract

Background: Breast cancer occurs because of malignant growth of breast tissue cells. Therapeutic targets such as WEE1 and PLK1 are safer for normal cells. Current treatment is not very optimal. Therefore, alternative treatment using plants are needed, red spinach, which has known can inhibit cell cycle, causing apoptosis. Drug discovery using conventional methods (in vitro and in vivo) requires a large amount of time and money, so in silico methods can be the solution. Objective: The aim of this research is to determine the potential of inhibiting WEE1 and PLK1 proteins using active compounds of red spinach against breast cancer using in silico method. Method: This research using SMILES and 3D structure of red spinach to predict biology activity using PASS Online through pa value and biology activity; physicochemical test using lipinski’s rule of five through molecular weight, log P, hydrogen bond donor, hydrogen bond acceptor, molar refractivity; pharmacokinetics prediction using pkCSM through caco-2 permeability, CNS permeability, CYP2D6 substrate, CYP2D6 inhibitor, renal OCT2 substrate; docking validation through RMSD value; molecular docking through binding affinity and ligand interaction. Results: The result of this research shows that 2,3,7,8-Tetrahydroxy-chromeno[5,4,3-cde]chromene-5,10-dione, 3-(3,4-Dihydroxycinnamoyl)quinic acid, 4′,5,7-Trihydroxyflavone, ascorbic acid, catechin, naringenin, and quercetin fulfilled biology activity prediction, physicochemical test, pharmacokinetics prediction, WEE1 and PLK1 docking validation had RMSD value 0,634 Å and 1,729 Å, and docking analysis that had binding pocket that indicating the inhibitory side of WEE1 and PLK1. Conclusion: The result of this research could be concluded that the active compounds of red spinach have inhibitory activity on WEE1 and PLK1 proteins, characterized by amino acid residues and binding affinity values that are more negative than native ligand and comparison.