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

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Thiosemicarbazone ligands are known for their diverse biological activities.
• Copper(I) complexes have emerged as promising candidates for therapeutic applications.
• Developing novel agents against neglected tropical diseases and resistant cancers is a global health priority.

Purpose of the Study:

• To synthesize and characterize novel heteroleptic copper(I) complexes incorporating phosphane and bioactive thiosemicarbazone ligands.
• To evaluate the in vitro anti-trypanosome activity against Trypanosoma cruzi.
• To assess the in vitro anticancer activity against human ovarian (OVCAR3) and prostate (PC3) cancer cell lines, along with their cytotoxicity on normal cells.

Main Methods:

• Synthesis of four new copper(I) complexes: [Cu(PP)(LL)][BF4].
• Characterization using classical analytical and spectroscopic techniques.
• In vitro evaluation of anti-parasitic, anti-cancer, and cytotoxic activities.

Main Results:

• The synthesized copper(I) complexes exhibited significant cytotoxicity against Trypanosoma cruzi and chemoresistant prostate PC3 cancer cells, outperforming benchmark drugs.
• High cellular internalization was observed in OVCAR3 cells, with dppe-containing complexes specifically inducing apoptosis.
• No significant production of reactive oxygen species was detected, suggesting a distinct mechanism of action.

Conclusions:

• The novel copper(I) complexes possess promising anti-trypanosome and anticancer properties.
• The dppe-containing complexes are particularly effective in inducing cancer cell death via apoptosis.
• These compounds represent potential lead candidates for developing new therapeutic strategies against parasitic infections and resistant cancers.