2. Academic Validation
  3. 1,2,4-Triazole-Acetamide Conjugates as hEGFR Inhibitors: Synthesis, Anticancer Evaluation, and In Silico Studies

1,2,4-Triazole-Acetamide Conjugates as hEGFR Inhibitors: Synthesis, Anticancer Evaluation, and In Silico Studies

  • Chem Biodivers. 2026 Jan;23(1):e03299. doi: 10.1002/cbdv.202503299.
Bahadır Bülbül 1,  Necla Kulabaş 2,  Merve Gürboğa 3,  Ozlem Bingöl Ozakpınar 3,  Ümmühan Çakmak 4,  Fulya Öz Tuncay 4,  Yakup Kolcuoğlu 4,  Mohit Agrawal 5,  Mujeeb Khan 6,  İlkay Küçükgüzel 7
Affiliations

Affiliations

  • 1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Düzce University, Konuralp Campus, Düzce, Türkiye.
  • 2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Marmara University, İstanbul, Türkiye.
  • 3 Department of Biochemistry, Faculty of Pharmacy, Marmara University, İstanbul, Türkiye.
  • 4 Department of Chemistry, Faculty of Science, Karadeniz Technical University, Trabzon, Türkiye.
  • 5 School of Medical & Allied Sciences, K. R. Mangalam University, Gurugram, India.
  • 6 Department of Pharmaceutical Chemistry, R. C. Patel Institute of Pharmaceutical Education and Research, Shirpur, India.
  • 7 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Fenerbahçe University, İstanbul, Türkiye.
PMID: 41532806 DOI: 10.1002/cbdv.202503299
Abstract

A 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 18, 19, and especially 24 showed notable antiproliferative effects, with compound 24 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 20 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 20 and 24 as promising candidates for further development as EGFR-targeted Anticancer agents.

Keywords

1,2,4‐triazoles; apoptosis; cancer; hEGFR inhibitors; molecular dynamics.

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