含氟姜黄素类似物的合成及其抑制酪氨酸酶活性研究

Synthesis and Inhibitory Activity on Tyrosinase of Curcumin Fluoro-analogues

以对氟苯乙酮与氟苯甲醛进行羟醛缩合反应,合成3种不对称含氟姜黄素类似物。对产物进行分离提纯,对合成物结构进行表征。以L-多巴为底物,测试合成物对酪氨酸酶的抑制作用。结果表明:3种不对称姜黄素类似物对酪氨酸酶的抑制效果均强于姜黄素。合成物1-(4-氟苯基)-3-(4-氟苯基)丙烯酮(A_3)对酪氨酸酶的半数抑制浓度IC_(50)为36.7μmol/L,其抑制作用是姜黄素(IC_(50)=95.7μmol/L)的2.6倍。探讨了合成物抑制酪氨酸酶活性的构效关系。

Three asymmetrical curcumin fluoro-analogues were synthesized based on the dehydration synthesis of aldol condensation. By using the right ways to separate and purify the products, the pure ones of asymmetrical curcumin analogues can be gotten. The compounds were characterized by TLC-thin layer chromatography, the measure of melting range, infrared spectroscopy and H-nuclear magnetic resonance. Using L-DOPA as the substrate, the inhibitory activity on Tyrosinase of the curcumin analogues was tested, all of them had stronger activity than curcumin. The ICs0 of 1 - （4- fluorophenyl） -3- （4-fluorophenyl） acrylketone （ A3 ） was 36.7μmol/L, the inhibitory activity of the compound A3 on Tyrosinase was even 2.6 times better than curcumin with ICsoof 95.7 μmoL/L. The structure-activity relationship of the curcumin analogues was discussed.