蛇床子素衍生物合成及其細胞毒性之研究

Abstract

蛇床子為繖形科蛇床屬植物蛇床(Cnidium monnieri(L.)CUSS)之乾燥成熟果實，屬於補益藥。在近代藥理研究方面，發現蛇床子中的香豆素類化合物蛇床子素（osthol）能誘導血癌細胞（HL-60）走向細胞凋亡2、3。所以我們選擇蛇床子素進行結構上的修飾並與薑黃素（curcumin）的部分結構形成的化合物ferulic acid結合合成出一系列的衍生物，進行抗癌細胞毒殺活性測試來探討其結構與活性的關係，發現osthol上的isoprenyl group對於抗癌活性有重要的影響，且isoprenyl group位於C8的位置對於抗癌活性有較好的表現。而3,4-olefinic bond對抗癌活性有影響，但作用機制不明。當化合物osthenol與demethylsuberosin接上ferulic acid形成衍生物（26）與（35），發現抗癌活性與IC50表現比蛇床子素要來的優異，可將其做為先導藥物發展出新的抗癌藥物。此外，因為薑黃素不僅在抗癌方面表現優異，對於抗發炎亦有不錯的表現，因此我們相信取薑黃素部分結構形成的化合物ferulic acid做為取代基所合成出來的一系列衍生物對於抗發炎也會有不錯的結果。

Cnidii fructus, the dried mature fruits of Cnidium monnieri (L.) Cusson (Umbelliferae), is used as a tonic agent in traditional Chinese medicine. In modern medical study，osthol could induce apoptosis in HL-60 cells 2, 3. So we choose osthol and feurlic acid to develop a series of derivatives. We used the derivatives to do the MTT assay test and to discuss the SAR, the result teld us the isoprenyl group and the 3,4-olefinic bond of osthol is essential for its activity，and the isoprenyl group at position 8 had the better cytotoxicity. When osthol and demethylsuberosin reacted with ferulic acid to form the derivatives of (26) and (35) have the better effect of anti-cancer and IC50 value than osthol. So the derivatives of (26) and (35) can be the lead compounds to develop the anticancer drug. Therefore, because curcumin not only had the good effect to anticancer, but also to anti- inflammation. So we believe the derivatives has the good effect to anti-inflammation.