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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 IC 50 = 1.52 µM and selectivity index = 15.24. Also, chalcone 2f showed significant cytotoxic activity with IC 50 = 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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New pyrazolone derivatives structurally related to celecoxib and FPL 62064 were synthesized and biologically evaluated for their inhibitory activity against cyclooxygenases (COXs) and 5‐lipoxygenase (5‐LOX) and their selectivity indices were calculated. The results showed that compounds 3f, 3h, 3l, and 3p have an excellent COX‐2 selectivity index. Moreover, they showed potent 5‐LOX inhibitory activity relative to celecoxib and zileuton, as positive controls. These promising candidates were further investigated for anti‐inflammatory activity using the carrageenan‐induced rat paw edema method and ulcerogenic liability. The results showed no ulceration, which implies their gastric safety profile. Moreover, these compounds were evaluated for prostaglandin (PGE2) production in rat serum. Molecular docking in the COX‐2 and 5‐LOX active sites was performed to rationalize their anti‐inflammatory activities. Strong binding interactions and effective docking scores were identified. The results indicated that these derivatives are good leads for dual‐acting COX‐2/5‐LOX inhibitors to be used as potent and safe anti‐inflammatory agents.

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