呋喃并呫吨酮衍生物的合成与生物活性研究  

Synthesis and Bioactivity of Furoxanthone Derivatives

作　　者：覃江克[1] 韩留玉[1] 兰文丽[1] 唐煌[1] 苏桂发[1] 戴支凯[2] 徐庆[2] 

机构地区：[1]广西师范大学化学化工学院药用资源化学与药物分子工程教育部重点实验室,桂林541004 [2]桂林医学院药理实验中心,桂林541004

出　　处：《化学学报》2009年第22期2597-2606,共10页Acta Chimica Sinica

基　　金：广西科技开发计划应用基础研究专项(No.0639030);广西师大科研基金资助项目

摘　　要：以水杨酸、间苯三酚为原料合成了1,3-二羟基呫吨酮,经醚化、环化反应得到1-羟基呋喃并呫吨酮3a和3b,再经Mannich反应合成了10个呋喃并呫吨酮衍生物4和5,接着通过季铵化反应得到相应的10个季铵盐6和7.运用IR、一维和二维NMR、MS、元素分析等对化合物进行了结构表征,考察了化合物4～7对乙酰胆碱酯酶的抑制作用及化合物6,7的抗癌活性.结果表明:化合物4～7对乙酰胆碱酯酶具有较好的抑制活性,IC50=2.0～12.4μmol/L;化合物6,7对肝癌(HepG2)、肺癌(SPC-A)、口腔上皮癌(KB)、乳腺癌(MCF-7)这四种癌细胞株的增殖均有抑制作用,其中化合物6c对癌细胞株HepG2、化合物7d对癌细胞株MCF-7的抑制作用最强,IC50分别为0.82和0.77μmol/L.The linearly and angularly isomeric furoxanthones 3a, 3b were synthesized by etherification and cyclization of 1,3-dihydroxylxanthone, which was synthesized from salicylic acid and phloroglucinol; then ten furoxanthone derivatives 4 and 5 were prepared via Mannich reaction of 3a, 3b, respectively, finally the ten corresponding quaternary ammonium salts 6 and 7 were obtained by quaternization of 4 and 5; the structures of the synthesized compounds were confirmed by IR, NMR, MS and elemental analysis. Acetylcholinesterase （ACHE） inhibitory activities of compounds 4-7 and anti-cancer activities of compounds 6, 7 were also investigated. The results indicated that compounds 4-7 were capable of inhibiting AChE in vitro with moderate to good activities, IC50=2.0- 12.4 μmol/L. MTT assay indicated that compounds 6, 7 possessed effectively inhibitory activity against the proliferation of four cancer cells, including HepG2 （liver cancer）, SPC-A （lung cancer）, KB （oral epithelial carcinoma） and MCF-7 （galactophore cancer）, among which 6c against HepG2 and 7d against MCF-7 had the highest inhibitory activities, with the IC50 being 0.82 and 0.77 μmol/L, respectively.

关 键 词：呫吨酮 呋喃并呫吨酮衍生物 合成 胆碱酯酶 抗癌活性 

分 类 号：TQ251.1[化学工程—有机化工]