Synthesis and Anticancer Activity of Ergosterol Peroxide 3-Carbamate Pyrazole Side-Chain Derivatives

AbstractFifteen ergosterol peroxide-3-carbamate pyrazole derivatives were successfully synthesized and evaluated their cytotoxicity in vitro against human lung cancer A549 cell line, human hepatocellular carcinoma HepG2 cell line, human breast cancer MCF-7 cell line and human hepatic LO2 cell lines. Among them, ergosterol peroxide-3-piperazine-1-ethyl-5-pyrazole showed a strong cytotoxicity with an IC50 of 3.01 mu M against HepG2 cells, which was 6-fold higher than that of ergosterol peroxide. Further study of the mechanisms suggests that ergosterol peroxide-3-piperazine-1-ethyl-5-pyrazole had a total apoptosis rate of 61.04% at a concentration of 6 mu M and promotes reactive oxygen species (ROS) production in a dose-dependent manner in HepG2 cells. These findings suggest that the apoptosis and the generation of ROS may be two key indicators of oxidative stress induced by ergosterol peroxide-3-piperazine-1-ethyl-5-pyrazole. Based on these results, we further explored the molecular docking between ergosterol peroxide-3-piperazine-1-ethyl-5-pyrazole and heat shock protein 90 (HSP90), discovering a strong binding affinity between them. This suggests that ergosterol peroxide-3-piperazine-1-ethyl-5-pyrazole may exert its antitumor effects through oxidative stress.