Structure-bioactivity relationship study on anticancer Pd and Pt complexes with aliphatic glycine derivative ligands

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• The development of novel metal-based anticancer agents is crucial for overcoming drug resistance and improving therapeutic outcomes.
• Understanding the structure-activity relationship of metal complexes is key to designing more effective chemotherapeutics.

Purpose of the Study:

• To synthesize and characterize novel palladium(II) and platinum(II) complexes incorporating N-isobutylglycine and cyclohexylglycine ligands.
• To investigate the in vitro anticancer activity, solubility, lipophilicity, and DNA binding interactions of these metal complexes.

Main Methods:

• Synthesis and characterization of six Pd(II)/Pt(II) complexes.
• Density Functional Theory (DFT) calculations for geometric validation.
• In vitro anticancer assays against HCT116, A549, and MCF7 cell lines.
• Spectroscopic techniques (absorption, fluorescence, circular dichroism) and docking simulations for DNA binding studies.

Main Results:

• All synthesized Pd/Pt complexes exhibited significant anticancer activity, surpassing that of carboplatin.
• Complexes 3 and 4 showed superior cytotoxicity compared to cisplatin against the HCT116 cell line, with complex 4 being more potent than oxaliplatin against MCF7 cells.
• Complexes demonstrated varying water solubility and lipophilicity, influencing their cellular accumulation.
• DNA binding studies confirmed intercalation and minor groove binding, consistent with docking simulations.

Conclusions:

• The synthesized Pd(II)/Pt(II) complexes possess promising anticancer properties with potential for clinical application.
• Ligand structure significantly influences complex solubility, lipophilicity, and anticancer efficacy.
• The observed DNA binding modes provide insights into the mechanism of action for these novel chemotherapeutic agents.