IN SILICO STUDY OF COMPOUNDS IN CARDAMOM AS RADIOPHARMACEUTICAL LIGANDS FOR BREAST CANCER THERAPY

• Main Author: Nurnahari, Naura
• Format: Theses
• Language: Indonesia
• Online Access: https://digilib.itb.ac.id/gdl/view/62934
• Institution: Institut Teknologi Bandung

Breast cancer is the most commonly diagnosed type of cancer in Indonesia and the second leading cause of death after lung cancer. Various kinds of therapy options to treat breast cancer, one of which is considered effective is using a radiopharmaceutical. Radiopharmaceuticals were chosen because of their ability to emit radiation and damage tumors from within the cell. To work on the right target requires a small molecule as radionuclide carrier which has a good affinity to the target. Cardamom extract was known to have multiply anticancer effects based on in vitro tests on breast cancer cells which indicate that certain compounds have a good affinity for breast cancer targets. Thus, screening was carried out on 46 compounds contained in cardamom through docking to breast cancer receptors: estrogen-?, -?, and progesterone. The docking results showed that the cardamonin had the best value of free binding energy, inhibition constant, and interaction for each target. Furthermore, cardamonin was modified by replacing hydrogen on carbon atom number 12 and 14 with one or two molecules of iodine. Redocking between labeled cardamonin with each target does not eliminate the affinity. Native ligands, cardamonin, and iodocardamonin were then simulated using molecular dynamics to determine the stability of their interactions. Molecular dynamics simulation for 100 ns showed that each compound remained on the binding site during the simulation and the RMSD graph shows the average stability of the ligands—estrogen-? complex reached at 10 ns, 40 ns for the ligands—estrogen-? complex, and 90 ns for the ligands—progesterone complex. The calculation of MMPBSA gives the value of the free binding energy in the native ligand complex, cardamonin, iodocardamonin (C12), (C14), and (C12, C14) against estrogen-? were 37.10; 20.55; 23.38; 24.14; and 19.93 kcal/mol, respectively. The free binding energy values for the native ligand, cardamonin, iodocardamonin (C12), (C14), and (C12, C14) against estrogen-? were 20.45; 21.69; 18.33; 18.26; and 20.93 kcal/mol, respectively. The free binding energy values for the native ligand, cardamonin, iodocardamonin (C12), (C14), and (C12, C14) against progesterone were 38.38; 18.09; 17.87; 26.78; and 23.49 kcal/mol, respectively. Based on the data obtained, it can be predicted that the cardamonin has potential to be used as a radiopharmaceutical ligand in breast cancer therapy.