2026-04-28T14:42:52Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/97772024-12-17T11:02:12Zcom_10259_3596com_10259_5086com_10259_2604col_10259_3597

Balsa, Lucía M. d30c3c8c-dca2-4143-a9ab-8352175d8fff 600 Ferraresi Curotto, V. . f7d526dc-f4e1-49a4-9b8c-22f9b031d7d2 600 Lavecchia, Martín José f03264b5-b4d8-4e0f-9d42-48b5645c1be5 600 Echevarría, Gustavo Alberto b3f78ff7-b795-4cf8-9f35-6e5e17bb5d77 600 Piro, Oscar Enrique d61bad4c-b7a0-4785-9eee-d1c6c98bbc1c 600 García Tojal, Javier 221 600 0000-0003-3816-0483 Pis Diez, Reinaldo dba891e7-f406-453b-9d51-6d4eb3d488cc 600 González Baró, Ana C. 8193c5ec-ef8e-4c67-bbe5-31596f1fbeb2 600 León, Ignacio E. 673276ff-bbee-4327-92be-002533b85470 600 2024-12-12T12:15:10Z 2024-12-12T12:15:10Z 2021-06 1477-9226 http://hdl.handle.net/10259/9777 10.1039/d1dt00869b 1477-9234 We report here the synthesis, crystal structure, characterization and anticancer activity of a copper(II)-hydrazone complex, [Cu(MeBHoVa)(H2O)2](NO3) (for short, CuHL), against human breast cancer cells on monolayer (2D) and spheroids/mammospheres (3D). The solid-state molecular structure of the complex has been determined by X-ray diffraction methods. The conformational space was searched and geometries were optimized both in the gas phase and including solvent effects by computational methods based on DFT. The compound has been characterized in the solid state and in solution by spectroscopic (FTIR, Raman, UV-vis) methods. The results were compared with those obtained for the hydrazone ligand and complemented with DFT calculations. Cell viability assays on MCF7 (IC50(CuHL) = 1.7 ± 0.1 μM, IC50(CDDP) = 42.0 ± 3.2 μM) and MDA-MB-231 (IC50(CuHL) = 1.6 ± 0.1 μM, IC50(CDDP) = 131.0 ± 18 μM) demonstrated that the complex displays higher antitumor activity than cisplatin (CDDP) on 2D and 3D human breast cancer cell models. Molecular docking and molecular dynamics simulations showed that CuHL could interacts with DNA, inducing a significant genotoxic effect on both breast cancer cells from 0.5 to 1 μM. On the other hand, CuHL increases the ROS production and induces cell programmed death on breast cancer cells at very low micromolar concentrations (0.5–1.0 μM). Moreover, the compound decreased the amount of breast CSCs on MCF7 and MDA-MB-231 cells reducing the percentage of CD44+/CD24−/low cells from 0.5 to 1.5 μM. In addition, CuHL overcame CDDP with an IC50 value 65-fold lower against breast multicellular spheroids ((IC50(CuHL) = 2.2 ± 0.3 μM, IC50(CDDP) = 125 ± 4.5 μM)). Finally, CuHL reduced mammosphere formation capacity, hence affecting the size and number of mammospheres and showing that the complex exhibits antitumor properties on monolayer (2D) and spheroids (3D) derived from human breast cancer cells. This work was supported by CONICET (PIP 0340 and 0651), UNLP (X041 and X857) and ANPCyT (PICT 2016-1574), Argentina. A. C. G. B., G. A. E., M. J. L., I. E. L., O. E. P. and R. P. D. are members of the Research Career of CONICET. V. F. C. is a member of the Technical Career of CONICET. LMB has a fellowship from CONICET. application/pdf eng Royal Society of Chemistry Dalton Transactions. 2021, V. , n. 28, p. 9812-9826 https://doi.org/10.1039/D1DT00869B Química inorgánica Química analítica Chemistry, Inorganic Chemistry, Analytic Anticancer activity of a new copper(ii) complex with a hydrazone ligand. Structural and spectroscopic characterization, computational simulations and cell mechanistic studies on 2D and 3D breast cancer cell models info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion info:eu-repo/semantics/openAccess Dalton Transactions 50 28 9812 9826 THUMBNAIL Balsa-DT_2021.pdf.jpg Balsa-DT_2021.pdf.jpg IM Thumbnail image/jpeg 3988 https://riubu.ubu.es/bitstream/10259/9777/3/Balsa-DT_2021.pdf.jpg 14fcbd52b786abcc77884f940319b88e MD5 3 LICENSE license.txt license.txt text/plain; charset=utf-8 1362 https://riubu.ubu.es/bitstream/10259/9777/2/license.txt 5d013bfa6e473ff0db22cd82a4d71a70 MD5 2 ORIGINAL Balsa-DT_2021.pdf Balsa-DT_2021.pdf application/pdf 1525524 https://riubu.ubu.es/bitstream/10259/9777/4/Balsa-DT_2021.pdf c17bd910cad2ab5f6090a4a2b5e3669c MD5 4 10259/9777 oai:riubu.ubu.es:10259/9777 2024-12-17 12:02:12.293 Repositorio Institucional de la Universidad de Burgos bubrep@ubu.es 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