Title:Computational Study of Imidazolylporphyrin Derivatives as a Radiopharmaceutical Ligand for Melanoma
VOLUME: 14 ISSUE: 3
Author(s):Fransiska Kurniawan*, Rahmana E. Kartasasmita, Naoki Yoshioka, Abdul Mutalib and Daryono H. Tjahjono*
Affiliation:School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132, Department of Applied Chemistry, Faculty Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223- 8522, Center for the Development of Radioisotops and Radiopharmaceuticals, P2RR BATAN, Tangerang 15310, School of Pharmacy, Bandung Institute of Technology, Jalan Ganesha 10, Bandung 40132
Keywords:FGF, ligand, melanoma, molecular docking, imidazolylporphyrin, radiopharmaceutical.
Abstract:Background: Melanoma is the most aggressive type of skin cancer. Metastatic melanoma is
extremely difficult to treat with current therapy methods such as surgery. On the other hand, it is a good
opportunity to develop a radiopharmaceutical using a radionuclide such as Technetium (Tc) for diagnostic
and Rhenium (Re) for therapeutic purposes. T3,4BCPP has been be used as a radioimaging agent
for melanoma cancers experimentally. The aim of the present research was to design new imidazolylporphyrin
derivatives with better selectivity and higher affinity than those of T3,4BCPP by molecular
modeling.
Methods: Eight types of Re- and Tc-labeled imidazolylporphyrins were docked to Fibroblast Growth
Factor Receptor 1 (FGFR1, PDB ID: 5AM6) using AutoDock 4.2. FGFR1 was simulated by Molecular
Dynamic (MD) simulation for 30 ns using NAMD 2.10 at 37 °C. The obtained conformations were then
applied in a molecular docking simulation. Dovitinib (natural ligand of FGFR1), Re- and Tc-T3, 4BCPP
were used as references.
Results: The MD simulation resulted in an RMSD of 3.8 Å. From all the studied imidazolylporphyrin
derivatives, Tc-cD3, 4BCPMIP and Re-cD3, 4BCPIP had the best docking parameter. Tc-cD3, 4BCPMIP
had a free binding energy of -4.06 kcal/mol, while that of Re-cD3, 4BCPIP was -4.35 kcal/mol.
Conclusion: It is concluded that cD3,4BCPMIP and cD3,4BCPIP are two potential candidate ligands
for a melanoma radiopharmaceutical kit.
