Copper(I)‐Thiosemicarbazone Complexes with Dual Anticancer and Antiparasitic Activity
Four 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‐nitrofurfurylid...
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Published in | ChemMedChem Vol. 18; no. 14; pp. e202300074 - n/a |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Germany
Wiley Subscription Services, Inc
17.07.2023
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Subjects | |
Online Access | Get full text |
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Summary: | Four 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 on Trypanosoma cruzi and 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 on T. cruzi and 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.
Inspired by the similarities between some features of cancer and parasitic infections, and on the potential of copper compounds as active agents to treat both types of disease, we developed a family of four Cu(I) complexes with various combinations of two phosphane ligands and two bioactive thiosemicarbazone derivatives. The results of biological studies illustrate the potential of these compounds as antiparasitic and anticancer agents. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1860-7179 1860-7187 |
DOI: | 10.1002/cmdc.202300074 |