Pyrazolylporphyrin Derivatives as New Potential Ligand for Melanoma Cancer Radiopharmaceutical Kit: In Silico Study

摘要

Melanoma is the most lethal skin cancer, and it is related to Fibroblast Growth Factor 2 (FGF2) which is important for survival and proliferation of melanocytes. Diagnosis and therapy of melanoma cancer can be performed applying radiopharmaceutical with appropriate ligand. The aim of this research was to obtain new pyrazolylporphyrin derivatives having more potency than T_(3,4)BCPP as ligand for melanoma cancer radiopharmaceutical kit. The proposed porphyrin derivatives are several combination of meso-substituent between (methyl-pyrazole)-4-yl and 3, 4-bis(carboxymethylenoxy)phenyl and combination of (1,2-dimethyl pyrazolium)-4-yl and 3, 4-bis(carboxymethylenoxy)phenyl. Nine types of pyrazolylporphyrin derivatives and their labeled-Rhenium (Re) and Technetium (Tc) were studied using molecular docking simulation on both active sites of FGF receptor (PDB ID: 1FQ9) using AutoDock 1.5.6 software. Re-T_(3, 4)BCPP and Tc-T_(3, 4)BCPP were used for comparison. From all studied pyrazolylporphyrin derivatives, the 5, 10, 15-tris-[3, 4-bis(carboxymethylenoxy) phenyl]-20-(methylpyrazole-4-yl)-porphyrin (Tr_(3, 4)BCPPzP) gave the best docking result. For 1st and 2nd active site, Re-Tr_(3, 4)BCPPzP has free binding energy values of -15.10 kcal/mol and -17.70 kcal/mol, respectively, while those of Tc-Tr_(3, 4)BCPPzP were -13.02 kcal/mol and -16.23 kcal/mol, respectively. It is shown that the non-cationic porphyrin has better affinity than the cationic one. Considering the results, it was concluded that Tr_(3, 4)BCPPzP is the most potential ligand for melanoma cancer radiopharmaceutical kit.