A series of co-crystals containing 5-fluorouracil as the active pharmaceutical ingredient were prepared via mechanochemical grinding and a normal solution method. Results indicate that both methods produced similar products, as verified by comparison of the X-ray powder diffraction patterns. Structural studies on this series of co-crystals revealed the non-ionic interactions present in the crystal lattice that form 1, 2, and 3-dimensional networks through persistent hydrogen bonds formed by certain functional groups; these may be used as templates to create new solid-state structures. Docking studies using the CDOCKER protocol in Discovery Studio Version 2.5 were used to investigate the potential anti-cancer activities of the novel co-crystals against a colorectal cancer target protein, human thymidylate synthase. The results were compared with a control ligand, dUMP, which is also found in the structure of the deposited protein model, 1HVY. A CDOCKER interaction energy of -34.65 kcal/mol compared to that of dUMP was calculated, indicating that these co-crystals are promising anti-cancer compounds.
Graphical Abstract
Developing a series of 5-fluorouracil co-crystals; synthesis, characterization and their potential anti-cancer from molecular docking. The colorectal cancer target protein used in this study, human thymidylate synthase (PDB: 1HVY, shown as a cartoon), showing the secondary structure. The ligands dUMP (red), co-crystals 1 (blue), 2 (green), 3 (yellow), and 4 (purple) are shown superimposed in the binding pocket.