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-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.

Automated summary

Four new Cu(I) complexes were synthesized and characterized, and their anti-trypanosome and anticancer activities were evaluated. The complexes showed higher cytotoxicity against T. cruzi and chemoresistant prostate PC3 cells compared to benchmark drugs nifurtimox and cisplatin. They also exhibited high cellular internalization and activation of apoptosis in ovarian OVCAR3 cells. However, the production of reactive oxygen species was not significant.