Design, Synthesis and Molecular Docking of New Thieno[2,3‑d]Pyrimidin‐4‐One Derivatives as Dual EGFR and FGFR Inhibitors

• DOI: 10.1002/ddr.70061
• Publication Date: 2025-02-06T11:04:44Z
• Authors: Sara Sultan; Samar S. Tawfik; Khalid B. Selim; Magda N.A. Nasr
• Keywords: Staurosporine; EGFR Inhibitors; Docking (animal)

ABSTRACT Novel thienopyrimidinone hybrids 5–25 were developed and synthesized as potential inhibitors of human EGFR FGFR. The in vitro antiproliferative action all compounds, towards the breast tumor cells MDA‐MB‐231 MCF‐7, was evaluated with doxorubicin serving a reference (IC 50 = 6.72 µM). Compound 23 demonstrated highest anti‐breast cancer efficacy against both cellular lines having IC ranging from 2.95 to 3.80 µM. enzyme inhibition FGFR by most active candidates 18 , 21 23–25 further evaluated. Compounds 25 best values 0.077 0.059 µM, respectively, comparison Erlotinib 0.04 In Staurosporine 0.024 µM), compounds 24 0.055 0.029 respectively. study molecular docking carried out among examine relation between binding pattern these catalytic sites their biological activity, whereas computational results aligned results. Finally, compound which found be dual inhibitor FGFR, tested for inducing apoptosis affecting arrest within G2/M phase well it screened measure its safety normal MCF10a value 47.16 µM contrast 18.86 Accordingly, could considered therapy.