Enhanced Anticancer Potential of Pd(II)-Thiosemicarbazone Complexes: Selectivity, Mechanisms, and 3D Models

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Oncology

Background:

• Cancer remains a significant global health burden, necessitating the development of novel chemotherapeutic agents.
• Palladium(II) complexes are being explored for their potential anticancer properties.

Purpose of the Study:

• To synthesize and characterize novel palladium(II) complexes incorporating triphenylphosphine and thiosemicarbazone ligands.
• To evaluate the in vitro cytotoxic effects and mechanisms of action of these complexes against various cancer cell lines.

Main Methods:

• Synthesis and full characterization of six [PdCl(PPh3)(TSC)] palladium(II) complexes using spectroscopic (NMR, FTIR, MS) and crystallographic (X-ray diffraction) techniques.
• In vitro evaluation of cytotoxicity using 2D and 3D cancer cell models.
• Assessment of cellular effects including clonogenic survival, wound healing, cell cycle progression, and apoptosis via flow cytometry.

Main Results:

• Palladium(II) complexes from the B family exhibited significantly higher cytotoxicity than the C family, with IC50 values below 1 µM for ovarian and approximately 2 µM for breast cancer cell lines.
• The most potent complex, PdB1, demonstrated superior potency and selectivity compared to cisplatin, with a high selectivity index towards non-tumor cells.
• Mechanistic studies indicated that PdB1 induces apoptosis, promotes cell disintegration, loss of adhesion, and nuclear fragmentation in 3D spheroid models.

Conclusions:

• The synthesized palladium(II) complexes, particularly PdB1, show significant therapeutic promise as potent and selective antineoplastic agents.
• These compounds are effective in complex tumor microenvironments and may overcome chemoresistance.
• Further investigation into PdB1 as a novel anticancer drug candidate is warranted.