(1E,4E)-1,5?(2,3-????????????)??-1,4-???-3-?????????????????θ????????о?

Synthesis of (1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one Analogs and Its Anti-gastric Cancer Activity In Vitro

??OBJECTIVE To explore the efficient and economical synthesis method of asymmetric monocarbonyl curcumin analogues(AMCACs), design and sgnthesize a series of B19(1E,4E)-1,5-bis(2,3-dimethoxyphenyl)penta-1,4-dien-3-one analogs to investigate their anti-gastric cancer activities in vitro.METHODS A series of asymmetric B19 analogues containing 2,3-dimethoxyphenyl were designed via the combination principle of medicinal chemistry, and obtained a method for synthesizing intermediate (E)-2-(2,3- dimethoxybenzylidene)cyclopentanone by one step catalyzed by L-proline. The targeted compounds were screened by MTT assay, and colony cloning experiments were used to further verify its anti-gastric cancer activity in vitro.RESULTS Ten novel target compounds were synthesized, and the structures were confirmed by LC-MS and ¹H-NMR spectral analysis. Among them, compound 6e had the highest inhibitory activity on the growth of gastric cancer cells SGC-7901 and BGC-823, whose IC₅₀ were 9.80 and 13.50 μmol·L^-1, respectively.CONCLUSION L-proline could be used as a catalyst to synthesize asymmetric monocarbonyl curcumin analogues efficiently and economically. Compound 6e could effectively inhibit the growth of gastric cancer cells in vitro, and its toxicity and inhibition mechanism of tumor cell growth need to be further studied.