Synthesis, Anti-Tumour, and Antibacterial Activities of Monocarbonyl Curcumin Analogues of Piperidones

Curcumin has anti-tumour and antibacterial effects. In this research, fourteen kinds of piperidone monocarbonyl curcumin analogues with 3,5-dimethylene-4-piperidone as the parent scaffold and halogen substitution on both sides of the benzene ring were synthesized by Claisen–Schmidt reaction, and their anti-tumour effect, mechanism, and antibacterial activity were investigated. It was found that a series of curcumin analogues has different degrees of anti-tumour and antibacterial dual activity. Among them, 2,5-2Cl, 2Br-5Cl, 2-Cl, 2-F, and benzaldehyde have strong broad-spectrum anti-tumour effects and have obvious selective inhibitory effects on A549 cells. The IC₅₀ value is less than 5 μmol/L. The five promising compounds, respectively, inhibited the expression of AKT and ERK to induce apoptosis of A549 cells to varying degrees. The newly synthesized analogues 2,5-2Cl and 2Br-5Cl had stronger inhibitory effects on the growth of A549 cells than other analogues, and they tended to mainly inhibit the expression of AKT and ERK, respectively. However, 2-Cl and 2-F have significantly better inhibitory effects on methicillin-resistant Staphylococcus aureus (MRSA) than antibiotics. Taken together, piperidone monocarbonyl curcumin analogues may be developed as good candidates for potential prevention and treatment of cancer and bacterial infection complications.