丹参酮ⅡA衍生物的合成与放射增敏活性测定

Synthesis of TanshinoneⅡΑ Derivatives and Their Radiosensitivity Against Hela Cells

目的对丹参酮ⅡA进行结构修饰,以期得到放射增敏效果较好的衍生物。方法通过曼尼希反应在丹参酮ⅡA的16位引入不同的小分子胺,通过EI-MS、1HNMR确证化合物结构,通过噻唑蓝(MTT)法测定其对Hela细胞的半数抑制浓度(IC50)及20%抑制浓度(IC20)值,初步评价几种衍生物的放射增敏活性。结果得到丹参酮的5个化合物,其中4个未见文献报道。其中3个进行了放射增敏活性测定,发现在16位引入芳香环的衍生物C5放射增敏效果增强。结论在16位引入芳香环可能是提高药物放射增敏活性的一种方式。

Objective Structure modification of Tanshinone ⅡA was performed in order to get tanshinone derivativeswith higher radiosensitivity. Methods Structure of Tanshinone ⅡA was modified via Mannich reaction by adding differentsmall amines at C16. The structures of the derivatives were confirmed through spectral data of EI-MS and 1 HNMR. The antiprolif-eration activities and radiosensitizing activity of Tanshinone ⅡA derivatives against Hela cells were evaluated by MTT assay atIC50 and IC20 . Results Five compounds were synthesized, four of which were new. Compound C5 with an aromatic nucleus in-serted at C16 had higher radiosensitivity than the prototype drug. Conclusion Adding an aromatic ring at position C16 of Tan-shinone ⅡA may be a good way for enhancing radiosensitizing activity.