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[摘要]
目的为研究冬凌草甲素的构效关系,对冬凌草甲素进行结构修饰,合成其衍生物,并评价其细胞毒活性。方法经常规提取分离得到冬凌草甲素(Ⅰ);
通过氧化和酰基化,制备冬凌草甲素衍生物,所获产物采用NMR和MS确证结构;
采用MTT法观察衍生物的细胞毒活性。结果制备了6个冬凌草甲素的衍生物,分别为14-乙酰基冬凌草甲素(Ⅱ)、1,14-二乙酰基冬凌草甲素(Ⅲ)、14-对甲苯磺酰基冬凌草甲素(Ⅳ)、1-氧代冬凌草甲素(Ⅴ)、14-乙酰基-1-氧代冬凌草甲素(Ⅵ)、14-对甲苯磺酰基-1-氧代冬凌草甲素(Ⅶ),其中化合物Ⅳ、Ⅵ、Ⅶ为3个新化合物。初步药理实验表明部分衍生物细胞毒活性高于冬凌草甲素。结论首次评价了1-氧代冬凌草甲素衍生物的细胞毒活性,其活性高于冬凌草甲素。
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[Abstract]
Objective In order to study the structure-activity relationship of oridonin,Some derivatives of oridonin were synthesized and their cytotoxicity activity was evaluated.Methods Oridonin (Ⅰ) was isolated and purified by silica gel column chromatography.The derivatives were synthesized from oridonin through oxidation and acylation.All compounds were confirmed by spectrum analyses and their cytotoxicity was evaluated by MTT method.Results Six compounds were obtained and identified as: 14-acetyl-oridonin(Ⅱ),1,14-diacetyl-oridonin(Ⅲ),14-p-tolylsulfonyl-oridonin(Ⅳ),1-oxo-oridonin(Ⅴ),14-acetyl-1-oxo-oridonin(Ⅵ),14-p-tolylsulfonyl-1-oxo-oridonin(Ⅶ).Among them compounds Ⅳ,Ⅵ,and Ⅶ were new compounds.Five compounds showed better cytotoxicity than oridonin.Conclusion The cytotoxicity of 1oxo oridonin derivatives is first evaluated and shows the stronger cytotoxicity than oridonin.
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