Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF- B signaling...

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Oncology

Background:

• Nuclear factor kappa B (NF-κB) signaling is a key regulator in physiological and pathological processes, including cancer.
• Non-canonical NF-κB pathways are implicated in cancer cell chemoresistance, highlighting NF-κB as a potential therapeutic target.
• Targeting NF-κB offers a strategy to modify tumor cell behavior and overcome treatment resistance.

Purpose of the Study:

• To design and synthesize novel pyrazolone-based ligands with potential NF-κB inhibitory activity.
• To evaluate the anticancer properties of these synthesized compounds.
• To investigate the mechanism of action, specifically targeting the NF-κB signaling pathway.

Main Methods:

• Synthesis of a series of pyrazolone-based bioactive ligands.
• Pharmacological screening using virtual screening techniques.
• In vitro anticancer assays (e.g., IC50 determination against MCF-7 cells).
• Molecular docking and molecular dynamics simulations to elucidate binding interactions and pathway targeting.

Main Results:

• The synthesized pyrazolones were evaluated for their potential to target the NF-κB pathway.
• Compound APAU demonstrated significant anticancer activity against MCF-7 cells, with an IC50 value of 30 μg/ml.
• Molecular docking confirmed that the pyrazolones inhibit cell proliferation by targeting the NF-κB signaling pathway.
• Molecular dynamics simulations indicated favorable stability and flexibility of the pyrazolone-based ligands.

Conclusions:

• Pyrazolone-based ligands represent a promising class of compounds for targeting the NF-κB pathway.
• APAU exhibits potent anticancer effects, suggesting its potential as a therapeutic agent for cancer treatment.
• These findings support the development of NF-κB inhibitors for cancer therapy, particularly for chemoresistant tumors.