New ternary iron(iii) aminobisphenolate hydroxyquinoline complexes as potential therapeutic agents.

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Cancer Biology

Background:

• Development of iron-based metallodrugs for therapeutic applications is an active area of research.
• Triple-negative breast cancer (MDA-MB-231) and cervical carcinoma (HeLa) are aggressive cancers with limited treatment options.
• Hydroxyquinoline derivatives have shown promise as co-ligands in metallodrug design.

Purpose of the Study:

• To synthesize and characterize novel mixed-ligand iron(iii) complexes for potential therapeutic use.
• To evaluate the in vitro anticancer activity of these complexes against human cancer cell lines.
• To investigate the mechanism of action, including DNA interaction and apoptosis induction.

Main Methods:

• Synthesis and full characterization of two new iron(iii) complexes, [Fe(L)(8HQ)] (1) and [Fe(L)(Cl8HQ)] (2), using a tripodal aminobisphenolate ligand and hydroxyquinoline co-ligands.
• Assessment of complex stability in aqueous solution and binding affinity to Human Serum Albumin (HSA).
• In vitro cytotoxicity assays (MDA-MB-231, HeLa), apoptosis studies (morphology, DNA condensation, TUNEL), DNA damage assays (COMET), and DNA cleavage activity.

Main Results:

• Complexes 1 and 2 exhibit stability in aqueous solution and significant binding to HSA.
• Both compounds show potent, dose-dependent cytotoxicity against MDA-MB-231 and HeLa cells, outperforming the free co-ligands.
• Treatment with complexes 1 and 2 induces apoptosis, genomic damage, and ROS generation, indicating a multi-faceted mechanism of action.

Conclusions:

• The synthesized iron(iii) complexes [Fe(L)(8HQ)] (1) and [Fe(L)(Cl8HQ)] (2) are promising anticancer drug candidates in the low micromolar range.
• These complexes are particularly effective against triple-negative breast cancer cells, addressing a critical unmet medical need.
• The compounds also display significant anti-Mycobacterium tuberculosis activity, suggesting a broad spectrum of biological applications.