Synthesis and biological evaluation of halogenated phenoxychalcones and their corresponding pyrazolines as cytotoxic agents in human breast cancer |
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| Authors: | Peter A Halim Rasha A Hassan Khaled O Mohamed Soha O Hassanin Mona G Khalil Amr M Abdou Eman O Osman |
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| Institution: | aPharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt;bBiochemistry Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt;cPharmacology and Toxicology Department, Faculty of Pharmacy, Modern University for Technology and Information, Cairo, Egypt;dDepartment of Microbiology and Immunology, National Research Centre, Dokki, Egypt |
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| 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. |
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| Keywords: | Halogenated chalcones diaryl ether pyrazoline ROS p38 MAPK breast cancer cell cycle profile |
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