1,2,4-Triazole Conjugates as HEGFR Inhibitors: Synthesis, Anticancer Evaluation, and in Silico Studies

Bulbul, BahadirKulabas, NeclaGurboga, MerveOzakpinar, Ozlem BingolCakmak, UmmuhanTuncay, Fulya OzKucukguzel, Ilkay2026-02-102026-02-1020261612-18721612-188010.1002/cbdv.2025032992-s2.0-105027347537https://doi.org/10.1002/cbdv.202503299Agrawal, Mohit/0000-0003-0200-7882; Cakmak, Ummuhan/0000-0001-8719-2436A series of novel 1,2,4-triazole-acetamide derivatives was synthesized and evaluated for anticancer and hEGFR inhibitory activity. The compounds were obtained via multistep synthesis and characterized by spectroscopic methods. Cytotoxicity was tested against PC-3, MCF-7, A549, and K562 cell lines. Compounds <bold>18</bold>, <bold>19</bold>, and especially <bold>24</bold> showed notable antiproliferative effects, with compound <bold>24</bold> exhibiting higher selectivity and potency than gefitinib. It also induced apoptosis and inhibited migration in A549 and PC-3 cells, while selectively promoting invasion in PC-3, suggesting EMT-related behavior. In vitro kinase assays revealed compound <bold>20</bold> as the most potent hEGFR inhibitor (IC50 = 43.8 +/- 1.3 nM). Molecular docking and 200 ns molecular dynamics simulations confirmed its stable interaction with EGFR, particularly involving Cys797. These findings highlight compounds <bold>20</bold> and <bold>24</bold> as promising candidates for further development as EGFR-targeted anticancer agents.eninfo:eu-repo/semantics/closedAccess1,2,4-TriazolesApoptosisCancerEGFR InhibitorsMolecular Dynamics1,2,4-Triazole Conjugates as HEGFR Inhibitors: Synthesis, Anticancer Evaluation, and in Silico StudiesArticle