Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer

Novel halogenated phenoxychalcones 2a-f and their corresponding N-acetylpyrazolines 3a-f were synthesised and evaluated for their anticancer activities against breast cancer cell line (MCF-7) and normal breast cell line (MCF-10a), compared with staurosporine. All compounds showed moderate to good cytotoxic activity when compared to control. Compound 2c was the most active, with IC50 = 1.52 mu M and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC50 = 1.87 mu M and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38 alpha MAPK) and phosphorylated enzyme in MCF-7 cells, suggesting its ability to decrease cell proliferation and survival. It also showed the ability to induce ROS in MCF-7 treated cells. Compound 2c exhibited apoptotic behaviour in MCF-7 cells due to cell accumulation in G2/M phase and elevation in late apoptosis 57.78-fold more than control. Docking studies showed that compounds 2c and 2f interact with p38alpha MAPK active sites.

Automated summary

Novel halogenated phenoxychalcones and their corresponding N-acetylpyrazolines were synthesized and evaluated for their anticancer activities. Compounds 2c and 2f showed strong cytotoxic activity and the ability to regulate cell proliferation and survival.