Synthesis, dark toxicity and induction of in vitro DNA photodamage by a tetra(4-nido-carboranylphenyl)porphyrin.
The total synthesis of tetra(4-carboranylphenyl)porphyrins 4 and 6 and their zinc(II) complexes 5 and 7 are described. These compounds were characterized by analytical and spectroscopic methods and, in the case of 5, by X-ray crystallography. The water-soluble nido-carboranylporphyrins 6 and 7 were found to have low dark toxicity towards V79 hamster lung fibroblast cells, using a clonogenic assay (50% colony survival, CS(50)>300 microM). Upon light activation nido-carboranylporphyrin 6 effectively induced DNA damage in vitro. Two different methods were used to assess the extent of DNA damage: the super-coiled to nicked DNA and the alkaline Comet assay using human leukemia K562 cells. Significant PDT-induced DNA damage was observed for porphyrin 6 using both assays, compared to light-only and porphyrin-only experiments. It is concluded that this type of nido-carboranylporphyrin is a promising sensitizer for both the boron neutron capture therapy and the photodynamic therapy of tumors.
Vicente
M G H
MG
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA. vicente@lsu.edu
Nurco
D J
DJ
Shetty
S J
SJ
Osterloh
J
J
Ventre
E
E
Hegde
V
V
Deutsch
W A
WA
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D018360:Crystallography, X-Ray; D004249:DNA Damage / Q000187:drug effects*; D003624:Darkness; D007202:Indicators and Reagents; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008958:Models, Molecular; D008968:Molecular Conformation; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*; D011166:Porphyrins / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity*
D007202:Indicators and Reagents; D017319:Photosensitizing Agents; D011166:Porphyrins; C474617:meso-tetra(4-(o-carboranyl)phenyl)porphyrin