Synthesis, antitumor activity evaluation of some new N-aroyl-α,β-unsaturated piperidones with fluorescence

Abstract

Novel N-aroyl-α,β-unsaturated piperidones, series 1, series 2 and series 3 (featuring 2-bromo-4,5-dimethoxybenzylidene, 4-dimethylaminobenzylidene and 4-trifluoromethylbenzylidene, respectively), were synthesized as candidate cytotoxins. Most of the compounds displayed potent cytotoxicity against the human neoplastic cell lines SK-BR-3, PG-BE1, NCI-H460, MIA PaCa-2 and SW1990 in vitro, and approximately 64% of the IC₅₀ values were lower than 5 μM. Among those tested, compound 1b of series 1, 3a, 3d and 3e of series 3 proved to be the most active. Importantly, 1b displayed marked inhibitory effects on tumor growth in vivo and had no apparent toxicity to mice; this was evaluated by a nude mouse PG-BE1 xenograft model. In addition, the fluorescent properties of compounds series 1–3 were investigated. The interesting fluorescence exhibited by these compounds could be useful for their visualization in tumor cells, permitting further studies on these α,β-unsaturated piperidones as candidates for novel fluorescent antitumor agents.

• Antitumor agents
• cytotoxicity
• fluorescence
• α,β-unsaturated piperidones
• xenograft model

Declaration of interest

Financial support of this work was from National Natural Science Foundation of China (No. 21402010), the Foundation of Shandong Province (Nos. ZR2014BL008, ZR2010HL065). The authors report no declarations of interest.

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Supplementary information