PMID- 32578983 OWN - NLM STAT- MEDLINE DCOM- 20201204 LR - 20201214 IS - 1520-510X (Electronic) IS - 0020-1669 (Linking) VI - 59 IP - 13 DP - 2020 Jul 6 TI - Copper Complexes with 1,10-Phenanthroline Derivatives: Underlying Factors Affecting Their Cytotoxicity. PG - 9116-9134 LID - 10.1021/acs.inorgchem.0c00925 [doi] AB - The interpretation of in vitro cytotoxicity data of Cu(II)-1,10-phenanthroline (phen) complexes normally does not take into account the speciation that complexes undergo in cell incubation media and its implications in cellular uptake and mechanisms of action. We synthesize and test the activity of several distinct Cu(II)-phen compounds; up to 24 h of incubation, the cytotoxic activity differs for the Cu complexes and the corresponding free ligands, but for longer incubation times (e.g., 72 h), all compounds display similar activity. Combining the use of several spectroscopic, spectrometric, and electrochemical techniques, the speciation of Cu-phen compounds in cell incubation media is evaluated, indicating that the originally added complex almost totally decomposed and that Cu(II) and phen are mainly bound to bovine serum albumin. Several methods are used to disclose relationships between structure, activity, speciation in incubation media, cellular uptake, distribution of Cu in cells, and cytotoxicity. Contrary to what is reported in most studies, we conclude that interaction with cell components and cell death involves the separate action of Cu ions and phen molecules, not [Cu(phen)(n)] species. This conclusion should similarly apply to many other Cu-ligand systems reported to date. FAU - Nunes, Patrique AU - Nunes P AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. FAU - Correia, Isabel AU - Correia I AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. FAU - Marques, Fernanda AU - Marques F AD - Centro de Ciencias e Tecnologias Nucleares and Departamento de Ciencias e Engenharia Nucleares, Instituto Superior Tecnico, Universidade de Lisboa, Estrada Nacional 10, 2695-066 Bobadela LRS, Portugal. FAU - Matos, Antonio Pedro AU - Matos AP AD - Centro de Investigacao Interdisciplinar Egas Moniz, Campus Universitario, Quinta da Granja, Monte de Caparica, 2829-511 Caparica, Portugal. FAU - Dos Santos, Margarida M C AU - Dos Santos MMC AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. FAU - Azevedo, Cristina G AU - Azevedo CG AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. FAU - Capelo, Jose-Luis AU - Capelo JL AD - LAVQ, REQUIMTE, Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. AD - PROTEOMASS Scientific Society, Madan Park, Rua dos Inventores, 2825-152 Caparica, Portugal. FAU - Santos, Hugo M AU - Santos HM AD - LAVQ, REQUIMTE, Departamento de Quimica, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal. AD - PROTEOMASS Scientific Society, Madan Park, Rua dos Inventores, 2825-152 Caparica, Portugal. FAU - Gama, Sofia AU - Gama S AD - Department of Analytical Chemistry, Faculty of Chemistry, University of Bialystok, ul. Ciolkowskiego 1K, 15-245 Bialystok, Poland. FAU - Pinheiro, Teresa AU - Pinheiro T AD - Institute for Bioengineering and Biosciences and Departamento de Engenharia e Ciencias Nucleares, Instituto Superior Tecnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001 Lisboa, Portugal. FAU - Cavaco, Isabel AU - Cavaco I AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. AD - Departamento de Quimica e Farmacia, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal. FAU - Pessoa, Joao Costa AU - Pessoa JC AUID- ORCID: 0000-0002-3978-9964 AD - Centro de Quimica Estrutural and Departamento de Engenharia Quimica, Instituto Superior Tecnico, Universidade de Lisboa, Av Rovisco Pais, 1049-001 Lisboa, Portugal. LA - eng PT - Journal Article DEP - 20200624 PL - United States TA - Inorg Chem JT - Inorganic chemistry JID - 0366543 RN - 0 (Antineoplastic Agents) RN - 0 (Coordination Complexes) RN - 0 (Ligands) RN - 0 (Phenanthrolines) RN - 27432CM55Q (Serum Albumin, Bovine) RN - 789U1901C5 (Copper) SB - IM MH - Animals MH - Antineoplastic Agents/chemical synthesis/metabolism/*pharmacology MH - Cattle MH - Cell Line, Tumor MH - Coordination Complexes/chemical synthesis/metabolism/*pharmacology MH - Copper/chemistry/metabolism/*pharmacology MH - Drug Screening Assays, Antitumor MH - Humans MH - Ligands MH - Phenanthrolines/chemical synthesis/metabolism/*pharmacology MH - Protein Binding MH - Serum Albumin, Bovine/metabolism EDAT- 2020/06/25 06:00 MHDA- 2020/12/15 06:00 CRDT- 2020/06/25 06:00 PHST- 2020/06/25 06:00 [pubmed] PHST- 2020/12/15 06:00 [medline] PHST- 2020/06/25 06:00 [entrez] AID - 10.1021/acs.inorgchem.0c00925 [doi] PST - ppublish SO - Inorg Chem. 2020 Jul 6;59(13):9116-9134. doi: 10.1021/acs.inorgchem.0c00925. Epub 2020 Jun 24.