2025/10/15 by Li Chen, Lian Chen, Zhonghui Lu +7
Biochemistry, Genetics and Molecular Biology · Chemistry · Medicine · #Apoptosis #Cancer #Cancer cell #Cell #Cell cycle #Drug #Drug resistance #Ferrocene Chemistry and Applications #Ferroptosis and cancer prognosis #Mitochondrion #Programmed cell death #RNA modifications and cancer #Viability assay
paper · doi:10.1021/acs.jmedchem.5c01888
openalex publication_date 2025/10/15 · openalex created_date 2025/10/16 · openalex updated_date 2026/08/01
Abstract Cancer therapy faces significant challenges due to drug resistance and the limitations of conventional treatments that primarily target single mechanisms such as apoptosis. Herein, we designed and synthesized a class of 1,2,4-triazolopyrimidinyl derivatives as multifunctional chemotherapeutic agents that trigger both ferroptosis and apoptosis. These compounds are very effective in reducing the viability of some cancer cell lines. Among them, compound 34 demonstrated a broad spectrum of antiproliferative effects against nine cancer cell lines. Compound 34 induced both ferroptosis and apoptosis by causing G2/M phase cell cycle arrest, disrupting mitochondrial membrane potentials, promoting lipid peroxidation, and increasing the levels of Ca2+ and Fe2+ through the activation of calcium/calmodulin signaling. Significantly, compound 34 suppressed tumor growth by 92% in A549 xenografts and 95% in A549/TAX xenografts with minimal toxicity. These findings might shape the rational design in a new wave of dually functioned drugs for the treatment of cancers.