Promising anticancer agents based on 8-hydroxyquinoline hydrazone copper(II) complexes.

Area of Science:

• Coordination Chemistry
• Medicinal Chemistry
• Materials Science

Background:

• Benzoylhydrazones are versatile ligands with potential biological applications.
• Copper complexes are explored for their catalytic and therapeutic properties.
• 8-Hydroxyquinoline derivatives are known for their chelating and bioactive characteristics.

Purpose of the Study:

• To synthesize and characterize novel copper(II) benzoylhydrazone complexes.
• To investigate the antiproliferative activity of these complexes against cancer cell lines.
• To elucidate the mechanism of action, including DNA interaction and oxidative stress induction.

Main Methods:

• Synthesis of benzoylhydrazone ligands and their copper(II) complexes.
• Characterization using elemental analysis, mass spectrometry, FTIR, UV-Vis, NMR, EPR, and X-ray diffraction.
• Evaluation of physicochemical properties (pKa, lipophilicity, solubility, formation constants, redox potentials) and biological activity (cytotoxicity, DNA binding, ROS generation, apoptosis induction).

Main Results:

• Successfully synthesized and characterized a series of benzoylhydrazone ligands (L1-8) and their copper(II) complexes (1-8).
• Complexes exhibit diverse structures, including trinuclear formulations, and demonstrate moderate-to-strong binding to bovine serum albumin.
• Copper(II) complexes show significant antiproliferative activity against melanoma and lung cancer cells, outperforming cisplatin in most cases. Compound 8 is particularly promising, inducing oxidative stress, DNA damage, and apoptosis.

Conclusions:

• The synthesized copper(II) benzoylhydrazone complexes represent a promising class of anticancer agents.
• Compound 8 exhibits potent anticancer properties, mediated by oxidative stress and DNA damage, leading to apoptosis.
• These findings warrant further investigation of compound 8 as a potential therapeutic candidate for cancer treatment.