Prediction of Antiosteoporosis Activity of Thirty-Nine Phytoestrogen Compounds in Estrogen Receptor-Dependent Manner Through In Silico Approach

Abstract

Osteoporosis is one of the health problems in postmenopausal women due to estrogen deficiency. Phytoestrogen compounds can be used as an alternative osteoporosis treatment because of their similarity in structure and activity to estrogen. This research was conducted to predict the antiosteoporosis activity of thirty-nine phytoestrogen compounds and raloxifene, a modern antiosteoporosis drug in silico. The first step of the study involved the analysis of physicochemical properties of thirty-nine compounds and raloxifene using the SwissADME web tool. Compounds that met the criteria of the physicochemical properties were then subjected to molecular docking using PyRx 0.8 software with the AutoDock Vina method. The results were analyzed using Biovia Discovery Studio Visualizer 2016 software to find one or more compounds that predicted ERβ agonists. Finally, a toxicity test using the pkCSM web tool on the predicted agonist compounds was conducted to determine the values of hepatoxicity, skin sensitization, and Ames toxicity. AdmetSAR2 web tool was also used to predict the LD50 class of toxicity. The results of this in silico study revealed that raloxifene and 23 compounds displayed agonist interaction toward ERβ, and two of these compounds, namely catechin and epicatechin, were predicted agonist to ERβ with binding values of-5.6 and-5.9 kcal/mol, respectively. These two compounds also showed the lowest toxicity. The finding from this research indicated that catechin and epicatechin are the most potent and non-toxic antiosteoporosis compounds among the 39 phytoestrogens.