2-取代硫醚-5-(3,4,5-三甲氧基苯基)-1,3,4-噻二唑类化合物的合成、结构与体外抗癌活性  

Synthesis, Structure and Antitumor Activity of 2-Alkylthio-5-(3,4,5-trimethoxyphenyl)-1,3,4-thiadiazole Compounds

作　　者：宋宝安[1] 陈才俊[1] 杨松[1] 金林红[1] 薛伟[1] 张素梅[1] 邹志辉[1] 胡德禹[1] 刘刚[1] 

机构地区：[1]贵州大学精细化工研究开发中心教育部绿色农药和农业生物工程重点实验室,贵阳550025

出　　处：《化学学报》2005年第18期1720-1726,共7页Acta Chimica Sinica

基　　金：国家973计划(No.2003CB1144004);国家自然科学基金(Nos.20442003;20362004);高等学校博士学科点专项科研基金(No.20040657003);教育部新世纪优秀人才计划(No.NCET04-0912)资助项目

摘　　要：以天然产物没食子酸为原料经醚化、酯化、酰肼化、成盐、闭环、硫醚化六步反应合成了6个2-取代硫醚-5-(3,4,5-三甲氧基苯基)-1,3,4-噻二唑类衍生物,釆用铟催化下水相合成目标化合物8,具有反应条件温和,合成收率高的特点;用IR,1HNMR,13CNMR和元素分析对各化合物进行了表征及结构确证,并用X射线单晶衍射法测定了化合物8a[2-(2-氯-5-吡啶甲基)硫醚-5-(3,4,5-三甲氧基苯基)-1,3,4-噻二唑]的晶体结构,采用MTT法进行了新化合物抑制PC3和BGC-823癌细胞体外试验,结果表明在5μmol?L-1浓度下化合物8e对PC3的抑制活性为55.71%.化合物8b对BGC-823细胞抑制活性为66.21%.Abstract Six new 2-alkylthio-5-（3,4,5-trimethoxyphenyl）-1,3,4-thiadiazole derivatives were synthesized from gallic acid by six steps： etherification, esterification, hydrazidation, salt formation, cyclization, and thioetherification. The synthesis of the title compounds catalyzed by indium in aqueous media was easy in process with high yield and environmental-friendliness. The products were characterized by elemental analysis, IR,^1H NMR and ^13C NMR spectra. The crystal structure of compound 8a was determined by X-ray diffraction analysis. 8a belongs to the monoclinic system with space group C2/c and cell dimensions of a= 1.5730（19） nm, b=0.5477 nm, c=4.2244 nm, β=92.015（6）°, V=3.6370（2） nm^3, Z=8, Dc= 1.497 g/cm^3,μ=0.463 mm^-1, F（000）= 1696, R1 =0.0783, wR2=0.1832. It was found that the title compounds 8 possess good antitumor activity to PC3 and BGC-823 cells in vitro by MTT method. For example, the antiproliferation activity of compound 8e to PC3 cells at the concentration of 5μmol·L^-1 at 48 h was 55.71% and the antiproliferation activity of compound 8b to BCJC-823 cells at the concentration of 5μmol·L^-1 at 48 h was 66.21%.

关 键 词：1 3 4-噻二唑 3 4 5-三甲氧基苯基 晶体结构 抗癌活性 唑类化合物 甲氧基苯基 反应合成 体外试验 硫醚 X射线单晶衍射法 

分 类 号：R914[医药卫生—药物化学]