Synthesis and DNA cleavage activity of 2-hydrazinyl-1,4,5,6-tetrahydropyrimidine containing hydroxy group.
Synthesis and DNA cleavage activity of 2-hydrazinyl-1,4,5,6-tetrahydropyrimidine containing hydroxy group.
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DOI：
10.1016/j.bmc.2009.05.044
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发表时间：
2009-07
影响因子：
3.5
通讯作者：
Y. Shao;Yong Ding;Zhao-Li Jia;Xiao-min Lu;Zhilong Ke;Weihong Xu;Guoyuan Lu
中科院分区：
文献类型：
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作者：
Y. Shao;Yong Ding;Zhao-Li Jia;Xiao-min Lu;Zhilong Ke;Weihong Xu;Guoyuan Lu
合成了2-肼基-1，4，5，6-四氢嘧啶-5-醇二盐酸盐2和2-肼基-4，5-二氢-1H-咪唑二盐酸盐1作为无金属DNA切割剂。琼脂糖凝胶电泳用于评估在1和2存在下质粒pUC 19 DNA切割活性。2的DNA切割效率与其相应的非羟基化合物1相比表现出显著的增加。2促进的DNA裂解动力学数据符合Michaelis-Menten型方程，kmax为0.0378±0.0013h− 1，比未催化的DNA加速106倍。加速是由亲核羟基的空间接近性和磷酸二酯的铵和/或胍基的亲电活化驱动的。对Hela细胞和人白血病HL-60细胞的体外细胞毒活性也进行了检测，2显示出比1更强的细胞毒活性。
2-Hydrazinyl-1,4,5,6-tetrahydropyrimidin-5-ol dihydrochloride 2, as well as 2-hydrazinyl-4,5-dihydro-1H-imidazole dihydrochloride 1, was synthesized as metal-free DNA cleaving agent. Agarose gel electrophoresis was used to assess the plasmid pUC 19 DNA cleavage activities in the presence of 1 and 2. DNA cleavage efficiency of 2 exhibits remarkable increases compared with its corresponding non-hydroxy compound 1. Kinetic data of DNA cleavage promoted by 2 fit to the Michaelis–Menten-type equation with kmaxof 0.0378±0.0013h−1giving 106-fold rate acceleration over uncatalyzed DNA. The acceleration is driven by the spatial proximity of the nucleophilic hydroxy group and the electrophilic activation for the phosphodiester by the ammonium and/or guanidinium groups. In vitro cytotoxic activities toward Hela cells and human leukemia HL-60 cells were also examined, and 2 exhibits stronger cytotoxic activities than 1.