Oxidative cleavage of DNA mediated by hybrid metalloporphyrin-ellipticine molecules and functionalized metalloporphyrin precursors.
The nuclease activity of functionalized metalloporphyrins 1-8 and hybrid metalloporphyrin-ellipticine molecules 10-16 in the presence of potassium monopersulfate (KHSO5) or magnesium monoperoxyphthalate (MMPP), water-soluble oxygen atom donors at physiological pH, toward double-stranded phi X174 DNA is reported. The DNA cleavage efficiency as a function of the nature of functionalized metalloporphyrins, the length of the linkage between the two parts of the hybrid molecule, viz., metalloporphyrin and 9-methoxyellipticine, the nature of the central metal atom (Mn, Fe, or Zn) the ionic strength, and the nature of the oxygen donor has been studied. Single-strand breaks (SSBs) are observed on double-stranded DNA with a short incubation time of 2 min in the presence of manganese derivatives of both metalloporphyrins and hybrid molecules. Owing to their cytotoxic and nuclease activity, these new water-soluble hybrid molecules may be considered as efficient bleomycin models based on cationic metalloporphyrins.
Ding
L
L
Laboratoire de Chimie de Coordination du CNRS, Toulouse, France.
Etemad-Moghadam
G
G
Meunier
B
B
D010584:Bacteriophage phi X 174 / Q000235:genetics; D004278:DNA, Superhelical / Q000187:drug effects* / Q000378:metabolism; D004279:DNA, Viral / Q000187:drug effects* / Q000378:metabolism; D003851:Deoxyribonucleases / Q000494:pharmacology*; D006868:Hydrolysis; D008665:Metalloporphyrins / Q000494:pharmacology*; D010100:Oxygen / Q000494:pharmacology*; D010545:Peroxides / Q000494:pharmacology*; D010795:Phthalic Acids; D011188:Potassium / Q000494:pharmacology; D017680:Potassium Compounds; D012995:Solubility; D013431:Sulfates / Q000494:pharmacology*; D014867:Water
D004278:DNA, Superhelical; D004279:DNA, Viral; D008665:Metalloporphyrins; D010545:Peroxides; D010795:Phthalic Acids; D017680:Potassium Compounds; D013431:Sulfates; D014867:Water; C009007:potassium persulfate; D003851:Deoxyribonucleases; D011188:Potassium; D010100:Oxygen; C044731:magnesium monoperoxyphthalate