Copper(I)‐Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity

Author:

Machado João Franco12,Marques Fernanda34,Pinheiro Teresa45,Villa de Brito Maria J.12,Scalese Gonzalo6,Pérez‐Díaz Leticia7,Otero Lucía6,António João P. M.8,Gambino Dinorah6,Morais Tânia S.12ORCID

Affiliation:

1. Centro de Química Estrutural Institute of Molecular Sciences Faculdade de Ciências Universidade de Lisboa Campo Grande 1749-016 Lisboa Portugal

2. Departamento de Química e Bioquímica Faculdade de Ciências Universidade de Lisboa Campo Grande 1749-016 Lisboa Portugal

3. Centro de Ciências e Tecnologias Nucleares Instituto Superior Técnico Universidade de Lisboa Estrada Nacional 2695-066 Bobadela LRS Portugal

4. Departamento de Engenharia e Ciências Nucleares Instituto Superior Técnico Universidade de Lisboa Estrada Nacional 2695-066 Bobadela LRS Portugal

5. iBB – Instituto de Bioengenharia e Biociências Instituto Superior Técnico Universidade de Lisboa Av. Rovisco Pais 1 1049-001 Lisboa Portugal

6. Área Química Inorgánica Facultad de Química Universidad de la República Gral. Flores 2124 11800 Montevideo Uruguay

7. Laboratorio de Interacciones Moleculares Facultad de Ciencias Universidad de la República Gral. Flores 2124 11800 Montevideo Uruguay

8. Research Institute for Medicines (iMed.ULisboa) Faculdade de Farmácia Universidade de Lisboa Av. Prof. Gama Pinto Lisboa 1649-003 Portugal

Abstract

AbstractFour new Cu(I) complexes of the general formula [Cu(PP)(LL)][BF4], in which PP is a phosphane ligand (triphenylphosphane or 1,2‐bis(diphenylphosphano)ethane (dppe)) and LL is a bioactive thiosemicarbazone ligand (4‐(methyl)‐1‐(5‐nitrofurfurylidene)thiosemicarbazone) or 4‐(ethyl)‐1‐(5‐nitrofurfurylidene)thiosemicarbazone) were synthesized and fully characterized by classical analytical and spectroscopic methods. The anti‐trypanosome and anticancer activities were investigated in vitro onTrypanosoma cruziand in two human cancer cell lines (ovarian OVCAR3 and prostate PC3). To test the selectivity toward parasites and cancer cells, the cytotoxicity on normal monkey kidney VERO and human dermal fibroblasts HDF cells was also evaluated. The new heteroleptic complexes were more cytotoxic onT. cruziand chemoresistant prostate PC3 cells than the benchmark drugs nifurtimox and cisplatin. The compounds also showed a high level of cellular internalization by the OVCAR3 cells and, in particular, those containing the dppe phosphane showed activation of the cell death mechanism via apoptosis. On the other hand, the production of reactive oxygen species induced by these complexes was not evident.

Publisher

Wiley

Subject

Organic Chemistry,General Pharmacology, Toxicology and Pharmaceutics,Molecular Medicine,Drug Discovery,Biochemistry,Pharmacology

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