IN SILICO STUDY OF COMPOUNDS IN GHOST BANGLE (ZINGIBER OTTENSII VAL.) AS ESTROGEN ALPHA INHIBITORS

• Main Author: Novita Andriyani, Yosi
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/76542
• Institution: Institut Teknologi Bandung

Cancer is the main cause of death in the world. One of the most common cancers in the world is breast cancer. Breast cancer occupies the second position in death cases after lung cancer. One of the drugs used in the treatment of breast cancer has a mechanism as an alpha estrogen receptor inhibitor. Eextract Z. ottensii is known to have an anticancer effect based on in vitro tests on breast cancer. This study aims to predict compounds in Z. ottensii that have the potential as alpha estrogen receptor inhibitors. Methods in this study were carried out in silico including docking simulations using AutoDock 4.2 software, physicochemical profile predictions based on Lipinski's Rule of Five, pharmacokinetic profile predictions including absorption and distribution on the Pre-ADME page, and molecular dynamics simulations using AMBER16 software. The docking simulation results for 34 test compounds showed that zerumbone, p-menth-2-en-1-ol, and linalool were the best docking compounds. The prediction of the physicochemical properties of the three compounds complies with Lipinski's Rule of Five so that it can be interpreted that these compounds have a good drug-likeness profile. Predictions of the absorption profile of Human Intestinal Absorption (HIA) and Caco-2 cell absorption showed that these three compounds had good absorption profiles, as well as distribution profiles of compounds p-menth-2-en1-ol, and linalool with a proportion >90% which is bound strongly bound to plasma protein, whereas in the zerumbone compound it is obtained that a percentage of <90% is bound weakly bound to plasma protein. Molecular dynamics simulations for 200 ns showed that the interaction of the three test compounds against the alpha estrogen receptor remained stable in the binding pocket. The results of the molecular dynamics simulation for 200 ns, the calculation of the bond free energy at the snapshot in the last 10 ns shows that the binding free energy value of the natural ligand (4- hydroxytamoxifen) and the reference compound (raloxifene) is -37.07 kcal/mol, respectively. -36.53 kcal/mol. The binding free energies of the zerumbone, p-menth-2- en-1-ol, and linalool compounds have bond free energies of -24.33 kcal/mol, -16.42 kcal/mol, -17.96, respectively kcal/mol, where the three test compounds do not have more negative bond free energies than natural ligands and comparator compounds. Based on the data obtained, it can be predicted that the compounds zerumbone, pmenth-2-en-1-ol, and linalool do not have a better affinity than natural ligands and comparator compounds, but have the potential to be modified or further developed as alpha estrogen inhibitors.