Discovery of novel 1,2,4-triazoles derivatives acting as NF1 activators against cervical cancer

The 1,2,4-triazole scaffold represents a class of bioactive molecules with distinctive physicochemical properties and broad-spectrum biological activities. Previous studies have explored compounds bearing triazole rings for their anti-tumor potential, while the specific activity of such small molecules against the human cervical squamous cell carcinoma line (SiHa) remains rarely reported. Herein, a series of novel triazole-based molecules were designed, synthesized, characterized, and evaluated for their inhibition of cancer cell lines especially SiHa cells proliferation in vitro. Among them, compound 7c exhibited anti-proliferative activity against SiHa cells in vitro and significant antitumor efficacy in mouse cervical cancer xenograft model in vivo. Additionally, it showed excellent selectivity against the SiHa cell line compared to other tumor cell lines and normal cell lines. Compound 7c could suppress colony formation and cell migration in vitro, and induce apoptosis in mouse cervical cancer cells through activating neurofibromin 1 (NF1), thereby inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway. These findings could provide a novel lead compound for the development of anti-cervical cancer drugs.