摘要
目的：为寻找新型抗肿瘤化合物和探讨糖环羟基对８Ｃｌ腺苷的抗肿瘤活性的影响，合成了腺苷的维甲类似物和８Ｃｌ腺苷衍生物。方法：对腺苷的８位和８Ｃｌ腺苷的糖环羟基进行了结构改造，以酰胺键和酯键在腺苷的８位连接了具共轭基团的肉桂酰基和苯甲酰基，得到腺苷的维甲类似物；对８Ｃｌ腺苷的５′羟基进行了甲磺酰化，硝基化以及氯代反应，得到了它的衍生物。结果：合成了（６～１２），（１６），（１８～２０）等１１个新化合物。结论：这些新化合物以ＨＬ６０，ＢＩＵ，ＫＢ细胞株的细胞毒为指标进行生物活性筛选，结果表明，８位取代基和５′羟基是影响腺苷类化合物细胞毒活性的重要药效基团。
AIM: In order to find new type of antitumor compounds and study the contribution of hydroxyl groups on the sugar part to the antitumor activity of 8 Cl adenosine, the retinoid analogs of adenosine and the derivatives of 8 Cl adenosine were synthesized. METHODS: Based on the antitumor activity and structural feature of 8 chloroadenosine and retinoic acid, modifications were made at positions 5′ and 8, (un)substituted cinnamoyl and benzoyl groups were bound at 8 position through amido and ester bonds, sulfonation and nitrosation at 5′ OH and its direct chlorination were conducted. RESULTS: Eleven new compounds were synthesized, they were (6～12), (16), (18～20). CONCLUSION: The cytotoxic activity to HL 60, BIU, and KB of the new compounds were not great. Modifications on the 5′ OH and other hydroxyl groups influenced the cytotoxic activities of 8 Cl adenosine significantly. It is sugested that the substitutions at position 8 and the hydroxyl groups on the sugar ring play an important role for the antitumor activity of adenosine analogs.
出处
《药学学报》
CAS
CSCD
北大核心
1999年第1期29-33,共5页
Acta Pharmaceutica Sinica
