New ternary Fe(III)-8-hydroxyquinoline-reduced Schiff base complexes as selective anticancer drug candidates

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Biochemistry

Background:

• Cancer prevalence necessitates novel therapeutic strategies beyond platinum-based drugs.
• Metal-based compounds offer alternative avenues for cancer treatment.
• Iron(III) complexes with mixed ligands present unique opportunities for drug development.

Purpose of the Study:

• Synthesize and characterize novel mixed-ligand Fe(III)-aminophenolate complexes.
• Evaluate the biological activity and selectivity of these complexes against various human cancer cell lines.
• Investigate the binding affinities of the complexes to key biomolecules like bovine serum albumin (BSA) and calf thymus DNA.

Main Methods:

• Synthesis and characterization of Fe(III) complexes using analytical and spectroscopic techniques.
• Assessment of biomolecular binding through spectroscopic methods and molecular docking.
• In vitro evaluation of cytotoxicity and selectivity using human cancer cell lines and a non-tumoral fibroblast line.

Main Results:

• Two octahedral Fe(III) complexes, [Fe(L)(8HQ)(H2O)] (1) and [Fe(L)(Cl8HQ)(H2O)] (2), were successfully synthesized and characterized.
• Complex 2 exhibited higher affinity for BSA and DNA compared to complex 1.
• Both complexes 1 and 2 demonstrated greater efficacy than cisplatin against breast, colorectal, and bone cancer cell lines.
• Complex 2 displayed significantly higher selectivity towards cancer cells, particularly bone cancer cells, with selectivity index (SI) values of 18.8.

Conclusions:

• Mixed-ligand Fe(III)-aminophenolate complexes, particularly complex 2, represent promising candidates for novel cancer therapeutics.
• The enhanced activity and selectivity of complex 2 warrant further investigation for clinical applications.
• These iron-based compounds offer a viable alternative to platinum-based chemotherapy, with potential for improved therapeutic outcomes.