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  3. Discovery of novel hydrazinyl thiazole derivatives as potent anticancer agents by inhibiting eIF4E/eIF4G interactions

Discovery of novel hydrazinyl thiazole derivatives as potent anticancer agents by inhibiting eIF4E/eIF4G interactions

  • Eur J Med Chem. 2025 Jun 26:297:117911. doi: 10.1016/j.ejmech.2025.117911.
Binrong Yao 1,  Chao Zhang 1,  Ze Ye 1,  Pengyun Li 1,  Junhai Xiao 2
Affiliations

Affiliations

  • 1 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; State Key Laboratory of National Security Specially Needed Medicines, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
  • 2 National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China; State Key Laboratory of National Security Specially Needed Medicines, Beijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. Electronic address: xiaojunhai@139.com.
PMID: 40592185 DOI: 10.1016/j.ejmech.2025.117911
Abstract

eIF4E overexpression is common in patients with various tumors. As a potential anti-cancer target, eIF4E has attracted extensive attention from researchers. Here we report the design, synthesis, biological activity of a series of novel hydrazinyl thiazole derivatives (A1-A42). Among them, the target compound A37 showed excellent antiproliferative activity against A549, Hela, HepG2 and MCF-7 cells and low cytotoxicity against HEK-293T cells. A37 has good affinity for eIF4E protein by molecular docking and SPR analyses. Furthermore, A37 played an antitumor role in multiple modes of action including regulating the activity of eIF4E by inhibiting the Ras/MAPK/eIF4E signaling pathway, Apoptosis and cell migration. In addition, A37 significantly suppressed the growth of HepG2 xenografts in nude mice and was relatively nontoxic to mice. These results suggest that A37 may be an effective, hypotoxicity inhibitor of eIF4E/eIF4G interaction for the clinical treatment of tumors.

Keywords

Anti-cancer; HepG2 xenografts; Hydrazinyl thiazole; Synthesis; eIF4E/eIF4G interaction.

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