Naphthyl-Substituted Ruthenium(II)-Arene Complexes: Exploring the Impact of Binding Modes on Cytotoxicity in Cancer...

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Ruthenium(II)-arene complexes are explored for their therapeutic potential.
• Naphthyl substitution offers a route to modify complex properties.
• Targeting cancer cells selectively is crucial for effective chemotherapy.

Purpose of the Study:

• To synthesize and characterize novel naphthyl-substituted ruthenium(II)-arene complexes.
• To evaluate the cytotoxic properties of these complexes against cancer cell lines.
• To investigate the interaction of the complexes with biological targets like DNA and proteins.

Main Methods:

• Synthesis and full characterization of ruthenium complexes using NMR spectroscopy.
• Evaluation of DNA and bovine serum albumin (BSA) binding affinities.
• Cytotoxicity assays (IC50 determination) against MCF-7, Caco-2, HepG2, and Vero cell lines.
• Molecular docking studies against BSA and EGFR variants (EGFRWT, EGFRT790M).
• Apoptosis induction analysis and Hirshfeld surface analysis for crystal structure insights.

Main Results:

• Novel ruthenium complex Ru3 was synthesized and characterized.
• Complexes exhibited varying binding affinities to DNA and BSA.
• Ru1-3 showed significant cytotoxicity against MCF-7 and Caco-2 cells, with Ru2 achieving an IC50 of 1.39 μg/mL against Caco-2.
• Ru2 demonstrated selectivity, with minimal activity against healthy Vero cells.
• Molecular docking revealed favorable interactions with BSA and EGFR targets.
• Complexes were observed to induce apoptosis in cancer cells.

Conclusions:

• Naphthyl-substituted ruthenium(II) complexes possess promising anticancer properties.
• The observed selective cytotoxicity and apoptosis-inducing effects warrant further research.
• These complexes represent potential candidates for the development of novel cancer therapeutics.