Synthesis and Anticancer Activities of Pyrazole-Thiadiazole-Based EGFR Inhibitors

Area of Science:

• Medicinal Chemistry
• Oncology
• Computational Chemistry

Background:

• Lung cancer is a leading cause of cancer mortality.
• Epidermal growth factor receptor (EGFR) is a key target in lung cancer therapy.
• EGFR inhibitors offer a promising treatment avenue.

Purpose of the Study:

• To develop novel EGFR inhibitors with thiadiazole and pyrazole scaffolds.
• To evaluate the in vitro and in silico activity of synthesized compounds against lung cancer cells.
• To identify potent inhibitors targeting EGFR.

Main Methods:

• In vitro cytotoxicity assays (MTT) and mitochondrial membrane potential (MMP) analysis.
• EGFR enzyme inhibition assays.
• Molecular docking and molecular dynamics simulations for in silico evaluation.

Main Results:

• Compounds 6d, 6g, and 6j exhibited inhibitory activity against the A549 lung cancer cell line.
• Compound 6g demonstrated significant MMP (80.93%) and potent EGFR inhibition (IC50 = 0.024 ± 0.002 μM).
• In silico studies supported the inhibitory potential of the synthesized compounds.

Conclusions:

• The novel thiadiazole and pyrazole derivatives are effective EGFR inhibitors.
• Compound 6g is a promising candidate for further development in lung cancer treatment.
• The study highlights the potential of these scaffolds for targeted cancer therapy.