Synthesis and DNA cleavage activity of 2-hydrazinyl-1,4,5,6-tetrahydropyrimidine containing hydroxy group.
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 k(max) of 0.0378+/-0.0013 h(-1) giving 10(6)-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.
Shao
Ying
Y
Department of Chemistry, State Key Laboratory of Coordination Chemistry, Nanjing University, Nanjing, PR China.
Ding
Yong
Y
Jia
Zhao-Li
ZL
Lu
Xiao-Min
XM
Ke
Zhi-Hong
ZH
Xu
Wei-Hong
WH
Lu
Guo-Yuan
GY
D049109:Cell Proliferation / Q000187:drug effects*; D004247:DNA / Q000032:analysis / Q000378:metabolism*; D053837:DNA Cleavage / Q000187:drug effects*; D055808:Drug Discovery; D004587:Electrophoresis, Agar Gel; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D009994:Osmolar Concentration; D010957:Plasmids / Q000032:analysis / Q000378:metabolism; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology*
C543312:2-hydrazinyl-1,4,5,6-tetrahydropyrimidin-5-ol; D006834:Hydrazines; D011743:Pyrimidines; D004247:DNA