异穿心莲内酯衍生物的合成及其抗肿瘤活性

Synthesis and Antitumor Activity of Isoandrographolide Compounds

目的:合成并表征了21个新的异穿心莲内酯衍生物,初步研究了部分异穿心莲内酯衍生物的抗肿瘤活性。方法:根据穿心莲内酯类似物具有的抗肿瘤活性以及穿心莲内酯的特征药效基团,对穿心莲内酯进行了新的药物设计和改造。通过使异穿心莲内酯与草酰氯或长链二元酸酰氯反应,接着与不同的醇类进行酯化反应或与不同胺类进行酰胺化反应方法,合成了21个新异穿心莲内酯二草酰酯类和酰胺类衍生物,所有新合成的化合物结构都通过了IR,1H NMR,MS光谱与元素分析鉴定;并用噻唑蓝法初步研究了部分化合物的抗肿瘤活性。结果:体外药理活性表明,有1个稳定的化合物和穿心莲内酯抗肿瘤活性相当。结论:该修饰方法达到了一定效果。

AIM： To synthesize and characterize the new isoandrogTapholide dioxalyl ester or dioxalyl amide derivatives and to study antitumor activity of some of the derivatives. METHODS： On the basis of the antitumor activity the structure characteristics of androgTapholide, 21 of the new isoandrographolide dioxalyl esters or dioxalyl amides were synthesized through the reaction of isoandrographolide with dioxalyl chloride, alcohols or amines. All of the compounds were identified by IR, ^1H NMR, MS spectra and elemental analysis. The antitumor activity of some of the compounds were primarily studied. RESULTS AND CONCLUSION： 3,19-di {（n-butylamine）carbonyl carboxyl}-O-iso-andrographolide was found to possess similar antitumor activity to andrographolide. Stuctural modification to andrographolide could lead to new chemical entity with the antitumor activity.