Ferrocene-Pyrazole Hybrid Induces Ferroptosis and Metabolic Disruption in Pancreatic Cancer.

Drugs with multiple anticancer mechanisms have shown promising applications in tumor treatment. Herein, we synthesized a series of ferrocene-pyrazole hybrids (8-11) to assess their anti-pancreatic cancer activities. Among them, compound 11 exhibited higher anti-cancer effects compared to other compounds and showed low toxicity to normal HK-2 cells. The hemolysis experiment shows that compound 11 exhibited low hemolytic activity. Proteomics and metabolomics studies have found that a total of 35 proteins and 58 metabolites (negative mode) showed significantly different abundances in BxPC-3 cells treated with 10 μM compound 11. Subsequent research unveiled that compound 11 eradicates pancreatic cancer cells through the activation of various mechanisms, including ferroptosis and metabolic pathways. These studies may stimulate the development of ferrocene-pyrazole hybrids and provide effective cancer treatment.