Synthesis, cellular uptake and animal toxicity of a tetra(carboranylphenyl)-tetrabenzoporphyrin.
A water-soluble nido-carboranyl-tetrabenzoporphyrin has been synthesized in 43% overall yield, by condensation of butanopyrrole with a carboranylbenzaldehyde, followed by metal insertion, oxidation, demetallation and deboronation reactions. This compound accumulated within human glioblastoma T98G cells to a significant higher extent than a structurally related nido-carboranylporphyrin, and localized preferentially in the cell lysosomes. Animal toxicity studies using male and female BALB/c mice revealed that both compounds are non-toxic even at a dose of 160 mg/kg, administered intraperitoneally as a single injection at a concentration of 4 mg/mL. It is concluded that the tetra(carboranylphenyl)-tetrabenzoporphyrin is a promising new sensitizer for the treatment of malignant tumors.
Gottumukkala
Vijay
V
Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.
Ongayi
Owendi
O
Baker
David G
DG
Lomax
Larry G
LG
Vicente
M Graça H
MG
D000818:Animals; D001896:Boron Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000633:toxicity; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005909:Glioblastoma / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000633:toxicity; D011166:Porphyrins / Q000138:chemical synthesis* / Q000493:pharmacokinetics* / Q000633:toxicity; D012995:Solubility; D014867:Water / Q000737:chemistry
D001896:Boron Compounds; D017319:Photosensitizing Agents; D011166:Porphyrins; C510461:nido-carboranyl-tetrabenzoporphyrin; D014867:Water