4-β-酯取代-4-脱氧-4′-去甲表鬼臼毒素衍生物的合成及其抗肿瘤活性  

SYNTHESIS AND ANTITUMOR ACTIVITY OF 4-β-ALKOXYLCARBONYL-4-DEOXY-4′-DEMETHYLEPIPODOPHYLLOTOXIN

作　　者：陈再新[1] 马维勇[1] 王金娣[2] 陈秀华[1] 张椿年[1] 

机构地区：[1]上海医药工业研究院,上海200040 [2]华东理工大学,上海200237

出　　处：《药学学报》2000年第5期353-357,共5页Acta Pharmaceutica Sinica

摘　　要：目的　寻找高效低毒的抗肿瘤药物。方法和结果　本文设计并合成了新的C4 位 β构型的酯取代的衍生物 38个 (II 1～II 38) ,并进行了体外对L12 10 细胞和KB细胞的抗肿瘤活性实验。结论　脂肪酯的活性强于芳香酯 ,其中以II 10的活性最强 ,超过etoposide 2个数量级。脂肪酯中主链不超过 3个碳原子的活性较好。在芳香酯中 ,苯环上连接吸电子基的化合物的活性稍强于连接有供电子基的化合物。AIM To search for more potential and lower toxicity antitumor drugs. METHODS AND RESULTS Thirty eight new 4 β ester substituted 4 deoxy 4′ demethylepipodophylotoxin derivatives(II 1～II 38) were designed and synthesized. All compounds were screened in vitro against L 1210 leukemia and KB cells. CONCLUSION Fatty esters showed higher activity than aromatic esters. II 10 exhibited the highest activity, which is more than 100 fold of etoposide. For fatty esters, the compounds with less than 3 carbons in the main chain have higher activity, while for aromatic esters, those having electron attracting substituents in the aromatic ring are more active.

关 键 词：鬼臼毒素 衍生物 抗肿瘤活性 合成 

分 类 号：R914.5[医药卫生—药物化学] R979.1[医药卫生—药学]