Pyrazole derivatives as potent EGFR inhibitors: synthesis, biological evaluation and in silico and biodistribution...

Aim: Synthesis of pyrazole derivatives as EGFR inhibitors. Materials & methods: Cytotoxicity and EGFR inhibitory effect were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and EGFR kits, respectively. The biodistribution of radioiodinated compound nanoparticles in tumor-bearing mice was studied. Results: The IC₅₀ values of compound 4a against HepG2 cells and EGFR were 0.15 ± 0.03 and 0.31 ± 0.008 μM, respectively, while those of erlotinib were 0.73 ± 0.04 and 0.11 ± 0.008 μM, respectively. The binding scores of compound 4a and erlotinib to EGFR were -9.52 and -10.23 Kcal/mol, respectively. The maximum tumor uptake of radioiodinated compound after intravenous nanoparticle injection was 6.7 ± 0.3% radioactivity/g. Conclusion: Compound 4a is a promising antitumor agent with a potential EGFR inhibitory effect.