新型含氟姜黄素类似物的合成、晶体结构及抗肿瘤活性  

Synthesis,Crystal Structure and Anti-tumor Properties of Fluorine-Containing Curcumin Analogues

作　　者：赵承光[1] 杨菊[1] 梁栋楼[1] 唐琴琴[1] 张翼[1] 梁广[1] 李校堃[1] 

机构地区：[1]温州医学院药学院浙江省生物技术制药工程重点实验室,温州325035

出　　处：《有机化学》2010年第2期289-294,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金(No.20802054);浙江省教育厅(No.20070992);温州市科技局(No.Y20080016)资助项目

摘　　要：采用活性基团拼接法将含氟苯甲醛与酮反应,合成了5个含氟单羰基姜黄素类似物,结构经IR,1HNMR及ESI-MS确认.对所合成的化合物进行了抗肿瘤活性测试(MTT法),结果表明,部分化合物对肿瘤细胞有较强的选择性抑制活性,其中2,6-二(4-氟亚苯基)环己酮(3a)和2,6-二(2-氟亚苯基)环己酮(3b)的抗肿瘤谱广,活性较好,就此对化合物3b作了单晶培养,并就晶体结构进行了X衍射分析.结构表明化合物3b属三斜晶系,空间群P-1.晶胞参数a=0.9222(2)nm,b=0.9732(2)nm,c=1.0127(2)nm,α=88.920(4)°,β=75.672(3)°,γ=62.404(3)°,V=0.7755(3)nm3,Z=2,Dc=1.329Mg?m-3,μ=0.097mm-1,F(000)=324,最终偏离因子R=0.0590,wR=0.1841.Five fluorine-containing curcumin analogues were synthesized by the aldol condensation of fluorine-containing benzaldehyde with ketones. Their structures were characterized by ^1H NMR, IR and ESI-MS techniques. The anti-tumor activities of the mono-carbonyl analogues were evaluated against seven different tumor cell lines by an MTT assay. The results suggest that the fluorine-containing compounds exhibit anti-proliferative activities against selected tumor cells. Among the presented compounds, the cyclohexanone-containing analogues exhibited better anti-tumor properties in wider spectrum than acetone and cyclopentanone-containing analogues did. Therefore, one of cyclohexanone-containing compounds 3b was further determined and analyzed using X-ray single-crystal diffraction. The crystal of compound 3b belongs to triclinic, space group P-I, with unit cell dimensions a=0.9222（2） nm, b=0.9732（2） nm, c= 1.0127（2） nm, α=88.920（4）°, β=75.672（3）°, y=62.404（3）°, V=0.7755（3） nm^3, Z=2. Dc= 1.329 Mg·m^-3,μ=0.097 mm^-1, F（000）=324. The final R=0.0590. wR=0.1841.

关 键 词：姜黄素类似物 合成 晶体结构 抗肿瘤活性 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学]