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

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, ¹H NMR, ¹³C NMR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%.

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

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) nm³, Z＝8, D_c＝1.497 g/cm³, ＝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 5 μmol?L^－1 at 48 h was 55.71% and the antiproliferation activity of compound 8b to BGC-823 cells at the concentration of 5 μmol?L^－1 at 48 h was 66.21%.