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The role of hydrogen bonds on the stability of anticancer drug compounds TG/uracil, TG/5-fluorouracil and TG/gimeracil

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The use of drug combinations can be useful in the treatment of various cancers. In this work, we studied the interaction of tegafur (TG) drug with uracil (U), 5-fluorouracil (FU), and gimeracil (GI) as anti-tumor drugs. The DFT calculations were carried out to determine the structural parameters, interaction energies, strength of interactions, physical and topological properties of the TG/U, TG/FU, and TG/GI complexes. The chemical reactivity of U, FU, and GI molecules to TG was investigated using the molecular quantum descriptors. From the results, intermolecular interactions in complexes are of the hydrogen bonding type. The Espinosa-Molins-Lecomte (EML) equation was used to calculate the energy of hydrogen bonds. The effect of binding sites on the strength of hydrogen bonds and the stability of complexes was investigated. To evaluate the electronic transfers in complexes, the natural bond orbital (NBO) analysis was performed. The strength and nature of interactions were determined by atoms in molecules (AIM) and reduced density gradient (RDG) analysis.

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Data availability

The data that support the findings of this study are available from the corresponding author, upon reasonable request.


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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by BM, MZ, and EZ. The first draft of the manuscript was written by BM and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Batoul Makiabadi.

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Makiabadi, B., Zakarianezhad, M. & Zeydabadi, E. The role of hydrogen bonds on the stability of anticancer drug compounds TG/uracil, TG/5-fluorouracil and TG/gimeracil. Struct Chem 34, 755–767 (2023).

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