Synthesis, In Vitro Anticancer Evaluation and Computational Screening of Novel Imidazo [4,5‐c] Pyridine Derivatives

Two libraries of hybrid molecules combining imidazo[4,5‐c]pyridine with isoxazole and urea functional groups were synthesized and characterized using techniques such as ¹H NMR, ¹³ C NMR, ¹⁹F NMR, HRMS, MS, FT‐IR, and elemental analysis. These compounds were evaluated for in vitro anticancer activity using the MTT assay against MCF‐7 (human breast adenocarcinoma) and A‐549 (lung cancer) cell lines. Several compounds showed significant anticancer potential, with IC₅₀ values ranging from 11.56 to 34.64 µM for A‐549 and 17.88 to 48.77 µM for MCF‐7, compared to standard drugs cisplatin and doxorubicin. Notably, a compound with a 3‐CF ₃ ‐phenyl group (3h) in the urea series demonstrated strong inhibition with an IC₅₀ of 11.56 ± 0.187 µM against A‐549 cells and moderate activity against MCF‐7 cells (IC₅₀ of 17.88 ± 0.235 µM). Molecular docking studies indicated favorable binding affinity to VEGFR2, EGFR and topoisomerase II, whereas pharmacokinetic evaluations confirmed favorable drug‐like properties, aligning with Lipinski's rule. Our study highlights these hybrid molecules as promising candidates for cancer therapy, underscoring their potential in medicinal chemistry.