Cu(II) complexes based on benzimidazole ligands: synthesis, characterization, DFT, molecular docking & bioactivity...

Area of Science:

• Inorganic Chemistry
• Medicinal Chemistry
• Computational Chemistry

Background:

• Lung cancer remains a leading global cause of cancer mortality.
• Increasing treatment resistance necessitates the development of novel anti-cancer drugs.
• Metal complexes offer a promising avenue for novel therapeutic strategies.

Purpose of the Study:

• To design and synthesize novel Copper(II) complexes for lung cancer treatment.
• To evaluate the in vitro cytotoxicity of these complexes against A549 lung cancer cells.
• To investigate the computational properties and molecular interactions of the complexes.

Main Methods:

• Synthesis of 2-aminomethyl benzimidazole and salicylaldehyde derivative-based ligands and their Cu(II) complexes.
• Density Functional Theory (DFT) calculations for reactivity assessment.
• Molecular docking simulations to predict interactions with MMP-9 protein.
• MTT assay for in vitro cytotoxicity evaluation against A549 cells.

Main Results:

• Efficient synthesis of ligands and 1:1 Cu(II) complexes.
• Both Cu(II) complexes exhibited significant cytotoxicity against A549 lung carcinoma cells, surpassing their parent ligands.
• DFT calculations indicated high reactivity due to a low HOMO-LUMO band gap.
• Molecular docking revealed favorable binding energies and interactions with the MMP-9 protein.

Conclusions:

• The synthesized Cu(II) complexes demonstrate promising in vitro antiproliferative activity against A549 lung cancer cells.
• The complex Cu(L1Br) shows particular promise as a potential candidate for future lung cancer drug development.
• Computational studies correlate well with in vitro experimental findings, supporting the mechanism of action.