Molecular Docking Study of Pramipexole Derivatives as Radiopharmaceutical Candidates for Brain Imaging

Abstract

Neurodegenerative diseases are a global priority disease. According to the World Health Organization (WHO), it is estimated that by 2050, there will be 152 million people with neurodegenerative diseases. Currently, the method used for brain imaging is PET/CT, with the most widely used radiopharmaceutical being 18F-FDG [7,8]. 18F-FDG is used to determine brain glucose metabolism, however the 18F-FDG does not have a specific receptor. Pramipexole compounds can cross the blood-brain barrier and have high specificity for dopamine receptors. By modifying and labelling the structure of pramipexole derivatives, it is expected to obtain pramipexole derivatives with a good affinity to the dopamine receptor. In order to reduce the risk of failure, radiation hazard, and research funds, in this research, a molecular docking study was carried out using the targeted docking method between dopamine receptor proteins and 22 pramipexole derivatives using AutoDock 4, GaussView software for structure preparation, Gaussian software for energy calculation, and Biovia Discovery Studio for structure visualization. The experimental results showed that the free binding energy of pramipexole derivatives for the dopamine receptor was obtained in the range of -2.81 to -5.84 kcal/mol. The best free binding energy value was obtained for compound PD-7, with a free binding energy value of -5.84 kcal/mol, while the RMSD value obtained was 0.6 A°, and amino acid residues that interacted with compound PD-7 among others: Leu347, Leu343, Tyr198, Leu199, Glu202, Phe201, and Val203 with hydrophobic and hydrogen bond interactions. The PD-7 compound was labeled using the radioisotope iodine-131 based on the free binding energy value. From the experimental results, compound 131I-PD-7 showed a free binding energy value of -4.66 kcal/mol and interacts with the similar amino acid residues as compound PD-7. These results indicate that the compound 131I-PD-7 is a potential candidate to be studied further as a radiopharmaceutical candidate for brain imaging.