Hydrolytically Stable Ti^IV-Hydrazone-Based Metallodrugs: Protein Interaction and Anticancer Potential

Area of Science:

• Coordination Chemistry
• Materials Science
• Medicinal Chemistry

Background:

• Hydrazone ligands are versatile building blocks in coordination chemistry.
• Titanium complexes have shown potential in various biological applications.
• Understanding metal-ligand interactions is crucial for developing new therapeutic agents.

Purpose of the Study:

• To synthesize and characterize novel titanium(IV) complexes with hydrazone ligands.
• To investigate the stability and biological interactions of these complexes.
• To evaluate their anticancer potential against selected cell lines.

Main Methods:

• Synthesis and characterization using elemental analysis, FT-IR, UV-vis, NMR, HR-ESI-MS, and X-ray crystallography.
• Aqueous stability studies in DMSO-d/D2O.
• Bovine serum albumin (BSA) interaction studies using fluorescence and absorption spectroscopy.
• In vitro anticancer activity assays against HeLa, A549, and NIH-3T3 cell lines.
• Apoptosis induction studies using confocal microscopy and flow cytometry.

Main Results:

• Three titanium(IV) complexes, [Ti(L1-3)2] (1-3), were successfully synthesized and structurally elucidated.
• Complexes 1-3 demonstrated good hydrolytic stability in a DMSO-d/D2O medium.
• High affinity for bovine serum albumin (BSA) was observed, indicated by static quenching.
• Complex 1 exhibited significant cytotoxicity against HeLa cells (IC50 = 11.6 ± 1.1 μM).
• The complexes were found to induce apoptosis, confirmed by microscopy and flow cytometry.

Conclusions:

• The synthesized titanium(IV)-hydrazone complexes are stable and interact strongly with BSA.
• Complex 1 shows promising anticancer activity and induces cell death via apoptosis.
• These findings highlight the potential of these complexes as anticancer agents.