Triphenylphosphine-Modified Iridium^III, Rhodium^III, and Ruthenium^II Complexes to Achieve Enhanced Anticancer...

Area of Science:

• Organometallic Chemistry
• Medicinal Chemistry
• Cancer Biology

Background:

• Organelle-targeting moieties enhance anticancer drug selectivity.
• Mitochondrial targeting is a promising strategy for cancer therapy.

Purpose of the Study:

• Synthesize and evaluate novel triphenylphosphine-modified iridium(III), rhodium(III), and ruthenium(II) complexes for targeted anticancer activity.
• Investigate the mechanism of action, focusing on mitochondrial targeting and downstream effects.

Main Methods:

• Synthesis and characterization of metal complexes.
• In vitro cytotoxicity assays against cancer (A549, HeLa) and normal (BEAS-2B) cell lines.
• Confocal microscopy and flow cytometry to assess mitochondrial targeting and function.
• Cell cycle analysis and wound-healing assays to evaluate antimigration effects.

Main Results:

• Triphenylphosphine-modified complexes displayed potent cytotoxicity (5.13–23.22 µM) against A549 and HeLa cells.
• High selectivity indices (7.3 to >19.5) were observed, indicating preferential toxicity to cancer cells.
• Complexes localized to mitochondria, depolarized mitochondrial membrane potential (MMP), and increased reactive oxygen species (ROS).
• Induction of G2/M cell cycle arrest and significant inhibition of cancer cell migration were observed.

Conclusions:

• Triphenylphosphine-modified metal complexes effectively target mitochondria, leading to cancer cell death.
• These complexes demonstrate promising anticancer efficacy and selectivity, warranting further investigation as potential therapeutic agents.