Design, Synthesis, Docking Studies, and Investigation of Dual EGFR/VEGFR‐2 Inhibitory Potentials of New Pyrazole and Pyrazolopyridine Derivatives

• DOI: 10.1002/ddr.70056
• Publication Date: 2025-02-05T11:25:56Z
• Authors: Shimaa M. Alhamaky; Nadia A. Khalil; Amr K. A. Bass; Nada Osama; Marwa S. A. Hassan
• Keywords: Pyrazole; Docking (animal); Lead compound

ABSTRACT The anticancer potential of certain newly synthesized pyrazole and pyrazolopyridine derivatives has been estimated. NCI 60 cancer cells cytotoxic screening pointed out compounds 3e 3f as the highest agents with % mean growth inhibition 67.69% 87.34%, respectively. five dose outcomes outlined most potent agent promising MG‐MID GI 50 = 3.3 µM when compared to erlotinib (MG‐MID 7.68 µM). In in vitro assays, 3d, 3e, 3f, 4a demonstrated dual inhibitory on EGFR WT VEGFR‐2 IC range 0.066−0.184 0.102−0.418 µM, best EGFR/VEGRF‐2 effect was shown by compound . Moreover, latter stopped cell cycle at G1/S phase. Also, it greatly boosted total apoptosis, including early late 54.5‐ 84.7‐fold, respectively, which supposes HCT‐116 death via inducing apoptosis. This confirmed elevation BAX caspase‐3 levels, decreased BCL‐2 level. safety active assessed results showed selectivity toward over FHC (selectivity index [SI]: 20.84) (SI: 3.42). Finally, efficient binding both enzymes, could explain sufficient level each enzyme.