DFT, Molecular Docking, Bioactivity and ADME Analyses of Vic-dioxim Ligand Containing Hydrazone Group and its Zn(II)...

Area of Science:

• Medicinal Chemistry
• Computational Chemistry
• Drug Discovery

Background:

• Cancer remains a leading global cause of death, necessitating the development of novel, targeted therapies with reduced toxicity.
• Identifying new anti-cancer agents with improved efficacy and safety profiles is a critical area of research.

Purpose of the Study:

• To evaluate the anti-cancer potential of novel vic-dioxime derivatives with a hydrazone group and their corresponding Zinc(II) complex.
• To utilize molecular docking, bioactivity, and quantum chemical calculations to assess their interaction with cancer-related targets.

Main Methods:

• Molecular docking simulations were conducted against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor 2 (VEGFR2).
• Density Functional Theory (DFT) was employed for molecular geometry optimization, frontier molecular orbital analysis, Mulliken charge distribution, and electron density mapping.
• In silico evaluation of bioactivity parameters and Absorption, Distribution, Metabolism, and Excretion (ADME) properties was performed.

Main Results:

• The Zn(II) complex exhibited higher binding affinity towards VEGFR2 and EGFR compared to the parent ligand (LH2).
• The Zn(II) complex demonstrated favorable ligand efficiency and fit quality for EGFR.
• Both LH2 and its Zn(II) complex satisfied Lipinski's Rule of Five, indicating good oral bioavailability potential.

Conclusions:

• The investigated vic-dioxime derivatives, particularly the Zn(II) complex, represent promising candidates for the development of targeted and low-toxicity anticancer drugs.
• These compounds warrant further investigation in preclinical and clinical studies for their therapeutic potential against cancer.