萘查耳酮类化合物的设计合成及对CYP1B1酶的抑制活性评价

目的:设计并合成几类新型的萘查耳酮衍生物,初步测定其对CYP1B1酶的抑制活性,筛选具有良好抗癌作用的CYP1B1抑制剂。方法:以1,5-二羟基萘为原料,首先合成两个重要的中间体2-乙酰基-1,4,5,8-四甲氧基萘、1,5,6-三甲氧基-2-萘乙酮,然后利用羟醛缩合反应合成所需要的化合物。结果:合成了19个目标化合物,其结构均经过核磁共振氢谱确证,所有化合物均为全新化合物。对所合成的新化合物均进行了EROD酶实验测定。结论:所合成的化合物均具有较强的CYP1B1酶一抑制活性,其中4-1、4-2、5'-1对CYP1B1的抑制活性强于CYP1B1强抑制剂α-萘黄酮(IC50=11 nmol/L),他们的IC50分别为6.5、0.47、8nmol/L。

Synthesis and CYP1B1 Inhibitory Activity of Benzo-chalcone Derivatives

Objective： A series ofbenzo-chalcone derivatives were designed and synthesized, and then they were tested for their C YP 1B 1 inhibitory activities to find some potent CYPI B 1 inhibitors which might have good anti cancer effects. Methods： 1, 5-dihydroxy- naphthalene was used as the starting material, then two important intermediates （2-acetyl-1, 4, 5, 8-tetramethoxy-naphthalene and 1, 5, 6 trimethoxy-2-acetonaphthone） were synthesized. Finally, target compounds were synthesized through aldol reaction. Results： Nineteen novel benzo-chalcone derivatives were synthesized, and their structures were confirmed by 1H-NMR. Moreover, their enzyme inhibitory activities were also tested through enzyme assay. Conclusion： The CYP1B 1 inhibitory activities of the target compounds were evaluated and the results demonstrated that most of them had potent inhibition against CYP 1B 1. Among all these compounds, 4-1, 4-2and 5＇-1 were the most potent CYP1B 1 inhibitors with the IC50 value of 6.5, 0.47, 8 nmol/L, which even better than α-naphthoflavone （IC50=1 1 nmol/L）.