两种去甲基斑蝥素衍生物的合成、^(125)I 标记及其动物体内分布

SYNTHESIS,LABELLING AND ANIMAL DISTRIBUTION OF TWO KINDS OF NORCANTHARIDIN DERIVATIVES

合成了两个新的去甲基斑蝥素衍生物Ｎ－甘氨基－５，６－二溴－７－氧双环［２．２．１］庚烷－２，３－二甲酰亚胺（ａ）和Ｎ－３，５－二溴酪氨基－５，６－二溴－７－氧双环［２．２．１］庚烷－２，３－二甲酰亚胺（ｂ），并对其进行了１２５Ｉ标记。最佳标记条件为：反应温度８０℃，ｐＨ＝６，标记反应时间３０ｍｉｎ。最高标记率分别达９５．４％和９１．６％。这两个新衍生物对癌细胞均有一定抑制作用，但衍生物ａ对癌细胞的抑制率较高，分别为２０．０％（ＫＢ），０（ＨＣＴ），５０．５％（Ｂｅｌ）。两种１２５Ｉ标记衍生物在小白鼠体内的分布实验表明，它们在其心、肝、肺、肾和脾中均有较高的浓集。两个新衍生物能否被癌细胞摄取有待进一步研究。

Two kinds of norcantharidin derivatives(a,b) are synthetized, then they are labelled by 125 I. The best labelling conditions are: labelling temperature 80 ℃,labelling time 30 min,pH=6. The labelling yields are 95.4% and 91.6%,respectively. The two derivatives have inhibition to the carcinoma cells. The derivative(a) has well antitumor activity, and the inhibition yields to KB, HCT and Bel are 20.0%, 0 and 50.5%,respectively.The animal distribution experiments show the derivatives have the high uptake in heart, liver,lung,kideney and spleen. It should be studied whether they can be uptaken by tumor.