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

Abstract

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 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC₅₀ = 1.87 µM and selectivity index = 11.03. Compound 2c decreased both total mitogen activated protein kinase (p38α 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.

Keywords:

• Halogenated chalcones
• diaryl ether
• pyrazoline
• ROS
• p38 MAPK
• breast cancer
• cell cycle profile

Acknowledgements

The authors thank Dr. Esam Rashwan, Head of the confirmatory diagnostic unit VACSERA-EGYPT, for carrying out cytotoxicity screening, cell cycle analysis, evaluation of ROS and p38 MAPK.

Disclosure statement

The authors declare that they have no conflicts of interest. The authors alone are responsible for the content and writing of this manuscript.