摘要
为提高海南新碱的抗肿瘤活性,研究其结构与活性的关系,设计合成了它的类似物。对其中活性较强的化合物8B进行了光学拆分,用同位素稀释法测定了(+)8B及(-)8B的光学纯度分别为96％及93％以上。用小鼠L_(1210)细胞软琼脂集落形成法测定了所有合成化合物的抗肿瘤活性,(-)8B的IC_(50)=1.9μmol/L,比先导物2a的活性提高18倍,并对构效关系进行了初步讨论。
A synthetic analogue of hainanensine 2a was further modified in order to improve
its antitumor activity. Six compounds 3～8,were obtained, and among these compounds 8 showed
significant activity. The diastereomer (±)8B was resolved by (+) tartaric acid and (-)benzoyl-tartar-
ic acid to the corresponding enantiomers (-)8B and (+)8B, respectively and their optical purities
were determined by isotope dilution method as 93% and 96%.
The antitumor activity of the newly obtained compounds were tested in vitro, and (-)8B was
found to have an IC_(50) of 1.9 mol/L, eighteen times higher than the original compound 2a.
出处
《药学学报》
CAS
CSCD
北大核心
1992年第11期824-829,共6页
Acta Pharmaceutica Sinica
关键词
海南新碱
类似物
抗肿瘤活性
化学
Hainanensine analogues
Resolution
Antitumor activity
