Synthesis and cellular studies of an octa-anionic 5,10,15,20-tetra[3,5-(nido-carboranylmethyl)phenyl]porphyrin (H(2)OCP) for application in BNCT

Bioorg Med Chem. 2005 Mar 1;13(5):1633-40. doi: 10.1016/j.bmc.2004.12.016.

Abstract

The total synthesis of 5,10,15,20-tetra[3,5-(carboranylmethyl)phenyl]porphyrins 2-5 containing 36-43% boron by weight are reported. All compounds were characterized by spectroscopic methods and, in the case of 2, by X-ray crystallography. The water-soluble nido-carboranylporphyrin 5 (H(2)OCP) was found to have low dark toxicity toward V79 lung fibroblasts (CS(50) > or = 250 microM), to be readily taken up by human glioblastoma T98G cells in culture and to localize subcellularly preferentially in the cell lysosomes. In comparison with a known tetra(nido-carboranyl)porphyrin (6), H(2)OCP (5) is taken up slower and to a lower extent by T98G cells, possibly as a result of its higher hydrophilic character. The metal-free H(2)OCP (5) was also found to accumulate to a higher extent in T98G cells compared with its zinc(II) complex analog 4. Our studies show that carboranylporphyrins bearing eight nido-carborane cages can still accumulate intracellularly and have low dark toxicity toward cells in culture, and therefore might have promise for application in BNCT.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Boron Neutron Capture Therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Cell Line
  • Cell Line, Tumor
  • Cricetinae
  • Crystallography, X-Ray
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Porphyrins / chemical synthesis*
  • Porphyrins / chemistry
  • Porphyrins / metabolism
  • Porphyrins / pharmacology*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Subcellular Fractions / metabolism

Substances

  • Porphyrins