Automated Radiosynthesis and Molecular Docking Studies of Coumarin- Triazole Hybrid with fluorine-18: A feasibility study

Background: Fluorine-18 is one of the promising radiotracers that can report target specific information related to its physiology to understand the disease status through the PET modality. In the current study, the radiochemical synthesis, purification, and molecular docking studies of fluorine-18 (18F) radiolabeled coumarin-triazole hybrid have been performed.

Objective: To develop target specific fluorine-18 radiotracer for the diagnosis in oncology.

Methods: GE Tracer-lab FX2N module with few modifications in the line connections was used for the radiosynthesis and purification of target molecule [¹⁸F]SG-2, 4-((2,6-dimethylmorpholino) methyl)-7-((1-(4-(fluoro-¹⁸F) benzyl)-1H-1,2,3-triazol-4-yl) oxy)-2H-chromen-2-one, through the nucleophilic radiofluorination mechanism. The radiochemical purity was measured by HPLC, and TLC analytical methods. The kryptofix levels were also evaluated by using the TLC method. The residual solvents like DMF, ethanol were measured using GC. The Schrödinger drug discovery suite 2018 was used to study the protein and ligand interactions.

Results: The quality control parameters revealed the purity, chemical identity, and limits of residual solvents. The radiochemical purity was 95.5 ± 2.3%, and dimethylformamide solvent limit was 89 ± 3 ppm. The molecular docking results had suggested that the cold target molecule has made strong electronic interactions and showed the possible pharmacokinetic (ADME) properties with galectin-1 protein. Overall, these results showed that [[¹⁸F]SG-2 radiolabeling with 18F radionuclide was feasible, and support of molecular docking studies suggest possible interactions with Galectin- 1.

Conclusion: we reported a feasibility study for labeling coumarin-triazole hybrid with fluorine-18 through aromatic nucleophilic fluorination reaction (S_NAr).