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Synthesis, DNA‐Binding, Cleavage, and Cytotoxic Activity of New 1,7‐Dioxa‐4,10‐diazacyclododecane Artificial Receptors Containing Bisguanidinoethyl or Diaminoethyl Double Side Arms
Author(s) -
Sheng Xin,
Lu XiaoMin,
Chen YueTing,
Lu GuoYuan,
Zhang JingJing,
Shao Ying,
Liu Fang,
Xu Qiang
Publication year - 2007
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200700549
Subject(s) - agarose gel electrophoresis , chemistry , dna , cleavage (geology) , stereochemistry , agarose , copper , biochemistry , biology , organic chemistry , paleontology , fracture (geology)
Novel 1,7‐dioxa‐4,10‐diazacyclododecane artificial receptors with two pendant aminoethyl ( 3 ) or guanidinoethyl ( 4 ) side arms have been synthesized. Spectroscopy, including fluorescence and CD spectroscopy, of the interactions of 3 , 4 , and their copper(II) complexes with calf thymus DNA indicated that the DNA binding affinity of these compounds follows the order Cu 2+ – 4 >Cu 2+ – 3 > 4 > 3 , and the binding constants of Cu 2+ – 3 are Cu 2+ – 4 are 7.2×10 4 and 8.7×10 4 M −1 , respectively. Assessment by agarose gel electrophoresis of the plasmid pUC 19 DNA cleavage activity in the presence of the receptors showed that the complexes Cu 2+ – 3 and Cu 2+ – 4 exhibit powerful supercoiled DNA cleavage efficiency. Kinetic data of DNA cleavage promoted by Cu 2+ – 3 and Cu 2+ – 4 under physiological conditions fit to a saturation kinetic profile with k max values of 0.865 and 0.596 h −1 , respectively, which give about 10 8 ‐fold rate acceleration over uncatalyzed supercoiled DNA. This acceleration is due to efficient cooperative catalysis of the copper(II) center and the functional (diamino or bisguanidinium) groups. In‐vitro cytotoxic activities toward murine melanoma B16 cells and human leukemia HL‐60 cells were also examined: Cu 2+ – 4 shows the highest activity with IC 50 values of 1.62×10 −4 and 1.19×10 −5 M , respectively.