New Platinum(II) Complexes Affecting Different Biomolecular Targets in Resistant Ovarian Carcinoma Cells

Area of Science:

• Medicinal Chemistry
• Oncology
• Drug Discovery

Background:

• Platinum-based chemotherapy is limited by drug resistance in ovarian cancer.
• Previous research identified platinum(II) complexes with triphenylphosphine as promising anticancer agents.

Purpose of the Study:

• To synthesize and evaluate novel brominated triphenylphosphine trans-platinum(II) derivatives.
• To assess the efficacy of these complexes against cisplatin-sensitive and resistant human ovarian cancer cell lines.
• To elucidate the mechanism of action and intracellular targets of the new platinum complexes.

Main Methods:

• Synthesis of two brominated triphenylphosphine trans-platinum(II) derivatives.
• In vitro evaluation of antiproliferative activity on human tumor cell lines.
• Assessment of intracellular accumulation and interaction with cellular targets.
• Analysis of DNA interaction, mitochondrial membrane potential, and intracellular redox state.
• Investigation of selectivity towards thioredoxin reductase.

Main Results:

• The novel platinum complexes demonstrated significant antiproliferative effects on resistant ovarian cancer cells.
• Remarkable intracellular accumulation of the complexes was observed.
• Evidence of DNA interaction, mitochondrial dysfunction, and altered cellular redox state was found.
• Selective interaction with the selenocysteine of thioredoxin reductase was identified.

Conclusions:

• The synthesized platinum(II) complexes exhibit potent activity against platinum-resistant ovarian cancer.
• Their mechanism involves intracellular accumulation, DNA interaction, mitochondrial disruption, and redox state impairment.
• These compounds represent potential candidates for overcoming platinum resistance in ovarian carcinoma treatment.