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5-Fluorouracil Co-crystals and Their Potential Anti-cancer Activities Calculated by Molecular Docking Studies

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Abstract

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.

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Acknowledgements

We appreciatively acknowledge Ministry of Higher Education of Malaysia and University of Malaya for the Exploratory Research Grant Scheme, ERGS (ER008-2013A), Fundamental Research Grant Scheme, FRGS (FP005-2015A), and Postgraduate Research Grant, PPP (PG054-2013B) and Computation and Informatics (C + i) Research Cluster/High Performance Scientific Computing Program (UMRG Project No. RP001C-13ICT) for their financial support.

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Authors and Affiliations

  1. Department of Chemistry, Faculty of Science, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Noor Izzati Nadzri, Nadia Hanim Sabri, Vannajan S. Lee & Siti Nadiah Abdul Halim

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  1. Noor Izzati Nadzri
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  2. Nadia Hanim Sabri
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  3. Vannajan S. Lee
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  4. Siti Nadiah Abdul Halim
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Correspondence to Siti Nadiah Abdul Halim.

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Nadzri, N.I., Sabri, N.H., Lee, V.S. et al. 5-Fluorouracil Co-crystals and Their Potential Anti-cancer Activities Calculated by Molecular Docking Studies. J Chem Crystallogr 46, 144–154 (2016). https://doi.org/10.1007/s10870-016-0638-y

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  • DOI: https://doi.org/10.1007/s10870-016-0638-y

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