xperimental 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 Cell

Author(s):Show less -

Leite, Celisnolia M. ^[1] ; Honorato, Joao ^[1] ; Martin, Ana Carolina B. M. ^[2] ; Silveira, Rafael G. ^[3] ; Colombari, Felippe M. ^[4] ; Amaral, Jessica C. ^[1] ; Costa, Analu R. . ^[1] ; Cominetti, Marcia R. . ^[5] ; Plutin, Ana M. ^[6] ; de Aguiar, Debora ^[3] ; Vaz, Boniek G. ^[3] ; Batista, Alzir ^{[1, 3]}

Affiliation

^[1] Univ Fed Sao Carlos UFSCar, Dept Quim, BR-13565905 Sao Carlos, SP - Brazil

^[2] Hosp Amor Barretos, BR-14784400 Barretos, SP - Brazil

^[3] Univ Fed Goias, Inst Quim, BR-74690900 Goiania, Go - Brazil

^[4] Ctr Nacl Pesq Energia & Mat, Lab Nacl Biorrenovaveis, BR-13083970 Campinas, SP - Brazil

^[5] Univ Fed Sao Carlos UFSCar, Dept Gerontol, BR-13565905 Sao Carlos, SP - Brazil

^[6] Univ Habana UH, Fac Quim, Lab Sint Org, Havana 10400 - Cuba

• Document type: Journal article
• Source: Inorganic Chemistry; DEC 2021.
• Web of Science Citations: 0

Abstract

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 stabi l i t y 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 react i v i t y 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. (AU)

• FAPESP's process: 21/04876-4 - Studies on structure & activity of RuII / arene / mercaptoligants complexes against cancer
• Grantee: João Honorato de Araujo Neto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/19342-2 - Metal complexes with dirivative ligands of lawsone and acylthioureas, with anticancer potential activities: study in vitro and in vivo.
• Grantee: Alzir Azevedo Batista
• Support Opportunities: Regular Research Grants