Experimental and theoretical DFT study of Cu(I)/N,N-disubstituted-N′-acylthioureato anticancer complexes: actin cytoskeleton and induction of death by apoptosis in triple-negative breast tumor cells

Leite, Celisnolia Morais; Araujo Neto, João Honorato de; Martin, Ana Carolina Baptista Moreno; Silveira, Rafael Gomes da; Colombari, Felippe Mariano; Amaral, Jéssica Cristina; Costa, Analu Rocha; Cominetti, Márcia Regina; Stevens, Ana María Plutín; Aguiar, Debora de; Vaz, Boniek Gontijo

Experimental and theoretical DFT study of Cu(I)/N,N-disubstituted-N′-acylthioureato anticancer complexes: actin cytoskeleton and induction of death by apoptosis in triple-negative breast tumor cells

Data

2022

Autores

Leite, Celisnolia Morais

Araujo Neto, João Honorato de

Martin, Ana Carolina Baptista Moreno

Silveira, Rafael Gomes da

Colombari, Felippe Mariano

Amaral, Jéssica Cristina

Costa, Analu Rocha

Cominetti, Márcia Regina

Stevens, Ana María Plutín

Aguiar, Debora de

Resumo

Six complexes with the general formula [Cu(acylthioureato)(PPh3)2] were synthesized and characterized using spectroscopic techniques (IR, UV/visible, and 1D and 2D NMR), mass spectrometry, elemental analysis, and X-ray diffraction. Interpretation of the in vitro cytotoxicity data of Cu(I) complexes took into account their stability in cell culture medium. DFT calculations showed that NMR properties, such as the shielding of carbon atoms, are affected by relativistic effects, supported by the ZORA Hamiltonian in the theoretical calculations. Additionally, the calculation of the energies of the frontier molecular orbitals predicted that the structural changes of the acylthiourea ligands did not cause marked changes in the reactivity descriptors. All complexes were cytotoxic to the evaluated tumor cell lines [MDA-MB-231 (triple-negative breast cancer, TNBC), MCF-7 (breast cancer), and A549 (lung cancer)]. In the MDA-MB-231 cell line, complex 1 significantly altered the cytoskeleton of the cells, reducing the density and promoting the condensation of F-actin filaments. In addition, the compound caused an increase in the percentage of cells in the fragmented DNA region (sub-G0) and induced cell death via the apoptotic pathway starting at the IC50 concentration. Taken together, the results show that complex 1 has cytotoxic and apoptotic effects on TNBC cells, which is a cell line originating from an aggressive, difficult-to-treat breast cancer.

Palavras-chave

Cells, Copper, Ligands, Metals

Citação

LEITE, Celisnolia M. et al. Experimental and theoretical DFT study of Cu(I)/N,N-disubstituted-N′-acylthioureato anticancer complexes: actin cytoskeleton and induction of death by apoptosis in triple-negative breast tumor cells. Inorganic Chemistry, Washington, v. 61, n. 1, p. 664-677, 2022. DOI: 10.1021/acs.inorgchem.1c03389. Disponível em: https://pubs.acs.org/doi/pdf/10.1021/acs.inorgchem.1c03389. Acesso em: 28 jun. 2023.