Study on molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM, HOMO-LUMO energies and docking studies of 5-fluorouracil, a substance used to treat cancer

Autor(es)

Almeida, Michell O. ; Barros, Daiane A. S. ; Araujo, Sheila C. ; Faria, Sergio H. D. M. ; Maltarollo, Vinicius G. ; Honorio, Kathia M.

• Tipo de documento: Artigo Científico
• Fonte: SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY; v. 184, p. 169-176, SEP 5 2017.
• Citações Web of Science: 6

Resumo

Cancer cells can expand to other parts of body through blood system and nodes from a mechanism known as metastasis. Due to the large annual growth of cancer cases, various biological targets have been studied and related to this disorder. A very interesting target related to cancer is human epidermal growth factor receptor 2 (HER2). In this study, we analyzed the main intermolecular interactions between a drug used in the cancer treatment (5fluorouracil) and HER2. Molecular modeling methods were also employed to assess the molecular structure, spectroscopic properties (FTIR and UV-Vis), NBO, QTAIM and HOMO-LUMO energies of 5-FU. From the docking simulations it was possible to analyze the interactions that occur between some residues in the binding site of HER2 and 5-FU. To validate the choice of basis set that was used in the NBO and QTAIM analyses, theoretical calculations were performed to obtain FT-IR and UV/Vis spectra, and the theoretical results are consistent with the experimental data, showing that the basis set chosen is suitable. For the maximum K from the theoretical calculation (254.89 nm) of UV/Vis, the electronic transition from HOMO to LUMO occurs at 4.89 eV. From NBO analyses, we observed interactions between Asp863 and 5-FU, i.e. the orbitals with high transfer of electrons are LP 015 (donor NBO) and BD{*} (pi) N-1-H-10 (acceptor NBO), being that the value of this interaction is 7.72 kcal/mol. Results from QTAIM indicate one main intermolecular H bond, which is necessary to stabilize the complex formed between the ligands and the biological target. Therefore, this study allowed a careful evaluation on the main structural, spectroscopic and electronic properties involved in the interaction between 5-FU and HERZ, an important biological complex related to the cancer treatment. (C) 2017 Elsevier B.V. All rights reserved. (AU)

• Processo FAPESP: 14/27189-9 - Estudo teórico da interação entre ligantes bioativos e o receptor TGF-² tipo 1 (ALK-5) empregando métodos de modelagem molecular
• Beneficiário: Michell de Oliveira Almeida
• Modalidade de apoio: Bolsas no Brasil - Doutorado