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

Abstract

Four new Cu(I) complexes of the general formula [Cu-(PP)(LL)][BF 4 ], 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-(5nitrofurfurylidene)thiosemicarbazone) or 4-(ethyl)-1-(5nitrofurfurylidene)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.

Cytotoxicity of copper(I) complexes containing indole‐based thiosemicarbazones and triphenylphosphine

“…The Cu(1)−S(2)−C(17)−N(5), Cu(1)−P(1)−C(33)−C(34) and Cu(1)−P(1)−C(39)−C(40) torsional angles were 170.83(14), 56.97(15), and 26.54(16)°, respectively. As mentioned earlier, the reports on copper(I) TSC complexes are quite rare [60–65,73] . Even in the presence of excess triphenylphosphine (as can be seen in Scheme 2), the copper(I) ion preferred to bind to two TSC ligands as observed by Dorairaj et al [73] …”

“…As mentioned earlier, the reports on copper(I) TSC complexes are quite rare. [60][61][62][63][64][65]73] Even in the presence of excess triphenylphosphine (as can be seen in Scheme 2), the copper(I) ion preferred to bind to two TSC ligands as observed by Dorairaj et al [73]…”

“…[52][53][54] There have been previous reports on indole-based TSCs conjugated with various metal ions as anticancer agents targeting numerous cancer cell lines, effectively inhibiting the proliferation and migration of cancer cells [55][56][57][58][59] but the ones with copper(I) are pretty scarce. [60][61][62][63][64][65] The copper(I) complexes with indole-based TSCs attracted our attention due to their possible anticancer action owing to their biologically active constituents. Herein, we used TSC derivatives that included indole fragment to develop copper(I) complexes for anticancer applications.…”

Copper(I) complexes of acylthiourea ligands: structural insights and cytotoxic potential

“…The anticancer efficacy, decreased toxicity, and ability to combat drug resistance action are all influenced by Cu's (Cu I/II ) redox behavior. 13,[32][33][34][35][36][37][38] There are several Cu complexes that were discovered to have anticancer properties. For instance, the Cu(II) complex of arylthiosemicarbazone ligand showed superior anticancer potential toward MDA-MB-231 breast cancer cells (IC 50 = 0.85 μM).…”

“…Cu(II) and Cu(I) ions attach to ceruloplasmin in the serum of living things to produce the active centers in the metalloprotein. The anticancer efficacy, decreased toxicity, and ability to combat drug resistance action are all influenced by Cu's (Cu I/II ) redox behavior 13,32–38 . There are several Cu complexes that were discovered to have anticancer properties.…”