新型土震素B类似物的合成及其生物活性的研究

 目的研究新型土震素B类似物的合成及其生物活性。方法以乙酰乙酸乙酯为起始物,设计合成了含2H-吡喃-2-酮结构的化合物10a～10l;采用MTT法测试细胞毒活性,用ELISA法测试胆碱酯酶抑制活性。结果合成的土震素B类似物及其各中间体通过1H-NMR,ESI-MS和IR确定其结构。生物活性测试中化合物10f对AchE的IC₅₀为6.98×10^-5mol·L^-1,所有目标化合物在4.0 g·L^-1对丁酰胆碱酯酶均无抑制作用。结论初步探明了化合物10f对乙酰胆碱酯酶有一定的抑制活性,并且发现该类化合物有较好的选择抑制活性。

Studies on Synthesis of New Territrem B Analogues and Their Biological Activities

OBJECTIVE To study the design and synthesis of new territrem B analogues and their biological evaluation.METHODS New territrem B analogues 10a～10l with the common structure of 2H-pyran-2-one were designed and synthesized from ethyl acetoacetate.The cytotoxicities and inhibitory activities on acetylcholinesterase and butylcholinesterase of these synthetic analogues were examined by MTT and ELISA methods,respectively.RESULTS New analogues of territrem B were afforded and the structures were confirmed by ¹H-NMR,ESI-MS and IR spectra.Compound 10f showed IC₅₀ value to acetylcholinesterase at 6.98×10^-5 mol·L^-1 and all target compounds showed no inhibition to butylcholinesterase at 4.0 g·L^-1.CONCLUSION The bioassay results indicated that 10f exhibited potential AChE inhibitory effect and better selectivity of AChE.