14-O-取代冬凌草甲素衍生物的合成及抗肿瘤活性(英文)

Synthesis and Anti-tumor Activity of 14-O-Derivatives of Natural Oridonin

目的:探索14-O-取代冬凌草甲素衍生物的合成及其抗肿瘤活性。方法:将二酸酐与冬凌草甲素14位羟基缩合,再与氨基酸酯进行酰胺化反应,合成14-O-取代冬凌草甲素衍生物;采用MTT法测试所有目标化合物体外对肿瘤细胞株(BGC-7901,SW-480,HL-60,BEL-7402,A549和B16)的细胞毒性以及化合物2c和2d对小鼠H22肝癌在体抗肿瘤活性。结果:合成了10个新的目标化合物,其结构均经IR,MS及1HNMR确证;生物活性初筛结果显示,化合物2c,2d和3e有较强的细胞毒活性;化合物2c和2d在体抗肿瘤活性大于环磷酰胺和冬凌草甲素。结论:14-O-取代冬凌草甲素衍生物2c,2d和3e作为潜在的抗肿瘤候选化合物值得进一步深入研究。

AIM： To synthesize novel 14-O-derivatives of natural oridonin and evaluate their anti-tumor activity. METHODS： Different anhydrides were conjugated with 14-hydroxyl and further reacted with amino acid esters via amidation. The cytotoxicity of derivatives against the human cancer cells BGC-7901, SW-480, HL-60, BEL-7402, A549 and BI6 in vitro were evaluated by MTT assay. The anti-tumor activity of 2c and 2d in mice with H22 liver tumor was tested in vivo. RESULTS： Ten novel compounds were synthesized and their structures were identified by IR, MS and ^1H NMR. The biological study results showed that compounds 2c, 2d, and 3e have potent cytotoxicity against the six cancer cell lines. Compounds 2c and 2d have stronger anti-tumor activity than oridonin and cyclophosphamide. CONCLUSION： As a possible result of the present findings, the 14-O-derivatives 2c, 2d and 3e of ofidonin as potential anticancer drug candidates may be worthy of further studies.