摘要
对4’-去甲表鬼臼毒素的C_4位进行化学修饰,合成和筛选了10个4-烷硫基-4-脱氧-4’-去甲表鬼臼毒素衍生物以进一步研究C_4位不同的原子和取代基与活性之间的关系及寻找结构简单、活性更强的抗肿瘤新药。4’-去甲表鬼臼毒素与硫醇在三氟化硼·乙醚或三氟乙酸存在下生成相应的硫醚,也可用硫醇与4β-溴-4-脱氧-4’-去甲表鬼臼毒素反应生成相应的硫醚。在体外筛选中,化合物10和12抑制L1210白血病细胞的活性与依托泊甙相当或更强,化合物9,10,12和15抑制KB细胞的活性与依托泊甙相当或更强。
As a continuing part of our study on the chemistry and antitumor activity of podo-phyllotoxin , 11 new C-4 S-substituted poclophyllotoxin derivatives were synthesised and screened invitro against L1210 leukemia and KB cells. Thus, 4′-demethylepipodophyllotoxin was reacted withthiols in the presence of BF_3.Et_2O or trifluroacetic acid to give thioethers. In addition, 4-bromo-4-de-oxy-4′-demethylepipodophyllotoxin, when reacted with thiols, also gave rise to correponding thioether(4-alkylthio-4-deoxy-4′-demethylepipodophyllotoxins). Compounds 10 and 12 have the same activityas etoposide in the inhibition against L1210 leukemia, and compounds g, 10, 12 and 15 also havecomparable activity with etoposide against KB cells.
出处
《药学学报》
CAS
CSCD
北大核心
1992年第9期656-661,共6页
Acta Pharmaceutica Sinica
关键词
鬼臼毒素
抗肿瘤活性
抗癌药
Podophyllotoxin derivative
Antitumor activity
