IN SILICO STUDY OF SECONDARY METABOLITES OF SPONGE AS POTENTIAL ESTROGEN RECEPTOR ALPHA INHIBITORS

• Main Author: Andre Reynaldi, Muhammad
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/62899
• Institution: Institut Teknologi Bandung

Estrogen receptor alpha is one of the receptors that acts as a drug target in the treatment of breast cancer. According to data from the World Health Organization (WHO) in 2020, there were 2.3 million women diagnosed with breast cancer and 685,000 deaths globally. One of the drug mechanisms in breast cancer is as an inhibitor of the alpha estrogen receptor. This study aims to obtain candidate guide compounds from various secondary metabolites in sponges that have the potential as inhibitors of the alpha estrogen receptor. This research method was carried out in silico, which consisted of docking simulation with Autodock 4.2 perangkat lunak, molecular dynamics with AMBER16 perangkat lunak and absorption and toxicity predictions via the ADMETlab website. Plakinamine A, Cacospongolide B, and Thorectandrol A were the best docking compounds with binding free energies of -12.34, respectively; -10.56; -10.22 kcal/mol. Prediction of human intestinal absorption (HIA) of the three compounds > 30%, which means that it is predicted to have good bioavailability and relatively non-toxic toxicity data. The conformation of the 3-dimensional structure resulting from the docking simulation of the three compounds was then studied by molecular dynamics simulation for 200 ns, where cacospongionolide B has a binding free energy of -37.43 kcal/mol, which is better than tamoksifen with a binding free energy of -28, 90 kcal/mol. Based on the analysis of the molecular dynamics simulation results, the interaction of cacospongionolide B with the receptor was relatively stable for 200 ns and remained in the binding pocket. Therefore, it can be predicted that the compound cacospongionolide B has potential as a guide compound for alpha estrogen receptor inhibitors.