In Silico and In Vitro Screening of 50 Curcumin Compounds as EGFR and NF-κB Inhibitors.

Area of Science:

• Medicinal Chemistry
• Computational Biology
• Oncology

Background:

• Cancer chemotherapy requires novel drugs due to limitations of current treatments.
• Curcumin, a natural compound, shows anticancer potential but has pharmacological limitations.
• Developing curcumin analogs is crucial for improving therapeutic efficacy.

Purpose of the Study:

• To evaluate the therapeutic potential of 50 novel curcumin derivatives.
• To calculate binding affinities of these derivatives to cancer-related targets: epidermal growth factor receptor (EGFR) and nuclear factor κB (NF-κB).
• To identify promising candidates for targeted cancer therapy.

Main Methods:

• Molecular docking simulations were employed to predict binding energies and constants.
• In silico results were validated using microscale thermophoresis.
• Bioactivity was assessed via resazurin cell viability, lactate dehydrogenase, reactive oxygen species, and annexin V/propidium iodide assays.

Main Results:

• Curcumin derivatives exhibited strong binding affinities to both EGFR and NF-κB, with energies ranging from -7.34 to -12.97 kcal/mol.
• Several derivatives showed significantly higher binding affinities than the parent curcumin compound.
• Binding was more stable for EGFR than for NF-κB, with 15 derivatives showing <−10 kcal/mol binding energy to EGFR.

Conclusions:

• Curcumin derivatization is a promising strategy for developing more effective and specific anticancer drugs.
• Molecular docking is a valuable tool for accelerating the identification of targeted curcumin-based cancer therapeutics.
• The study identified potent curcumin analogs for further preclinical and clinical investigation.