腺苷的结构改造与细胞毒活性研究

目的： 为寻找新型抗肿瘤化合物和探讨糖环羟基对8-Cl-腺苷的抗肿瘤活性的影响，合成了腺苷的维甲类似物和8-Cl-腺苷衍生物。方法： 对腺苷的8位和8-Cl-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8-Cl-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HL-60，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。

STRUCTURAL MODIFICATION AND CYTOTOXIC ACTIVITY OF ADENOSINE

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.