3,3'-(取代苯亚甲基)双(吲哚-2-甲酸乙酯)的微波合成及抗肿瘤活性

Microwave irradiation synthesis and antitumor activity of diethyl 3,3'-(substituted benzylidene)bis(1H-indole-2-carboxylate)

以吲哚-2-甲酸乙酯和取代苯甲醛为主要原料,三氟甲基磺酸铋为催化剂,利用微波辐射技术,设计制备了10种新型3,3’-(取代苯亚甲基)双(吲哚-2-甲酸乙酯)衍生物(3a~3j),产物结构经1H-NMR、13C-NMR、ESI-MS和元素分析确证。通过考察微波功率、反应时间、溶剂、催化剂及原料摩尔比等因素,筛选了最佳反应条件。利用溶剂缓慢挥发法,得到了3a、3d、3f、3g和3h五个化合物的单晶。通过细胞毒性试验,筛选出了先导化合物3d,其对A549细胞的IC_(50)值为7.14μmol·L^(-1),优于标准抗癌药物顺铂对A549细胞的IC_(50)值(36μmol·L^(-1)),具有成为叶酸靶向抗肿瘤药物的应用潜力.

In this work,ten novel compounds of diethyl 3,3'-(substituted benzylidene)bis(1H-indole-2-carboxylate)derivatives(3a~3j)were designed and synthesized by using bismuth trifluoromethyl sulfonate as catalyst under microwave irradiation.Indole-2-ethyl formate and substituted benzaldehyde were used as main materials.Their structures were confirmed by^(1)H NMR,^(13)C NMR and ESI-MS analysis.The optimized reaction conditions were established by examination of microwave power,reaction time,solvents,catalysts and molar ratio of raw materials.The single crystals of compounds 3a,3d,3f,3g and 3h were obtained by slow solvent evaporation method.The lead compound 3d was screened by cytotoxicity test.Its IC_(50) value against A549 cells was 7.14μmol·L^(-1),which was better than that of the standard anti-cancer drug cisplatin(36μmol·L^(-1)).It showed the potential to be used as folic acid-targeted anti-tumor drug.