Synthesis of a Boronated Derivative of Gd-Texaphyrine for Potential Use in Boron Neutron Capture Therapy (BNCT)

H. Ebrahimabadi, K; Najafi, R

Synthesis of a Boronated Derivative of Gd-Texaphyrine for Potential Use in Boron Neutron Capture Therapy (BNCT)

Document Type : Research Paper

Authors

k H. Ebrahimabadi

R Najafi

Abstract

In the last two decades treatment of brain tumors using BNCT has been performed using improved boron compounds and neutron irradiation techniques. Compounds that make use of carborane clusters, which have a high inherent boron content, should be more effective, provided, of course, the efficient and selective uptake of the boron-containing carrier molecules by cancer or other target cells. Examples of carborane cluster are the icosahedral C₂B₁₀H₁₂ carboranes. Many porphyrins and porphyrinoid compounds have demonstrated an ability to selectively accumulate in tumors, and have therefore been considered as the possible candidates for delivery of boron to malignant tissue. The texaphyrins are aromatic pentadentate macro cyclic expanded porphyrins, which have been found to be useful as MRI contrast agents, as radiation sensitizers and in photodynamic theraphy (PDT). In this study, a new boronated texaphyrine for potential use in BNCT has been proposed and synthesized.

Highlights

M. Graca, H. Vicente, “Syntheses of carbon-carbon linked carboranylated porphyrins for boron neutron capture therapy of cancer,” Tetrahydron letters. 41, 7623-7627 (2000(.

A. H. Soloway, W. Tjanks, B. A. Barnum, “The chemistry of neutron capture therapy,” Chem. Rev. 98, 1515-1562 (1998).
R. J. Fiel, E. Mark, “Mechanism of the localization of manganese(III) Meso-Tetra(4-Sulfonatophenyl) porphyrine in mice bearing L1210 tumors,” Cancer Letters, 40, 23-32 (1998).
F. Megnin, P. J. Faustino, “Studies on the mechanism of selective retention of porphyrins and metalloporphyrins by cancer cells,” Biochimica et Biophysica Acta, 929, 173-181 (1978).
J. L. Sessler and R. A. Miller, “Texaphyrins; New drugs with diverse clinical application in radiation and photodynamic Therapy,” Biochemical Pharmacology. 59, 733-734 (2000).
E. P. Kyba, R. E. Davis, C. W. Hudson, A. M. John, S. B. Brown, L. K. Mephaul. A. C. Glover, “Tetradentate 14-membered tetra-phosphino-containing macrocycles,” J. Am. Chem. Soc, 103, 3868-3875 (1981).
J. L. Sessler, V. Lynch, M. R. Johnson, “Synthesis and Crystal Structure of a novel Tripyrran-Containing Porphyrinogen-like macrocycle,” J. Org. Chem. 52, 4394-4397 (1987).
J. L. Sessler, G. Hemmi, T. D. Mody, T. Murai, A. Burreil, S. W. young, “Texaphyrins: Synthesis and Applications,” Acc. Chem. Res. 27, 43-50 (1994).
P. S. Clezy, C. Y. Fookes, J. A. Liepa, “The chemistry of pyrrolic compounds,”Aust. J. Chem. 25, 1979-1990 (1972).
C. P. Wong, “[5, 10, 15, 20-Tetraphenylporphyrinato (2-)] Lantanides and [5, 10, 15, 20- Tetraphenylporphyrinato(2-)] Actinides,” Inorg. Syn. 22, 156-162 (1983).

J. L. Sessler, T. Murai, G. Hemmi, “A water-stable Gd(III) complex derived from a new pentadentate expanded porphyrin ligand. Inorg. ,” Chem. 28, 3390-3393 (1989).
S. W. Young, K. W. Woodburn, M. Wright, “Lutetium Texaphyrin (PCI-0123): A near-infrared, water-soluble photosensitizer,” Photochemistry and Photbiology, 63(6), 892-897, (1996).
J. L. sessler, N. A. Tvermoes, D. G. Guldi, T. D. Mody, W. E. Allen, “One-electron reduction and oxidation sensitizer Gd(III) Texaphyrin (PCI-0120) and other water soluble metallotexaphyrins,” J. Phys. Chem. A. 103, 787-794, (1999).
F. Alanazi, H. Li, S. Oie, D. R. Lu, “Synthesis of carborane mimics of cholestrol ester and studies of there liposomsl formulations for targeted drug delivery,” J. Pharm. Sci. (2002), (Submit).
J. L. Sessler, W. E. Allen, V. A. Kral, “Highly boronated derivatives of texaphyrins,” US. Patent 5955586 (1999).
Ninth International Symposium on Neutron Capture Therapy for cancer, Osaka International Convention Center, Osaka, Japan, 334P, October 2-6 (2000).
J. L. Sessler and R. A. Miller, “Biochem. Pharm. texaphyrins; new drugs with diverse clinical application in radiation and photodynamic therapy,” Biochem. Pharm. 59, 733-739 (2000).
J. L. Sessler and T. Murai, “An expanded porphyrin: the synthesis and structure of a new aromatic pentadentate ligand,” J. Am. Chem. Soc. 110, 5586-5588 (1988).
D. Magda, C. Lee, J. Sessler, “Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species,” Int. J. Radiat. Oncol. Biol. Phys. 51, No. 4, 1025-1036 (2001).
S. Xu and K. Zakian, “Effect of motexafin Gd on tumor metabolism and radiation sensivity,” Int. J. Rad. Onc. Biol. Phys. 49, No. 5, 1381-1390 (2001).
J. L. Sessler, T. D. Mody, “Gd(III) Texaphyrin: A novel MRI contrast agent,” J. Am. Chem. Soc. 115, 10368-10369 (1993).
D. I. Rosenthal and P.Nurenberg, “A phase I single-dose trial of Gd-Tex, a tumor selective radiation sensitizer detectible by MRI,” Clinical Cancer Res. 5, 739-745 (1999).

Keywords

BNCT

Gd-Tex

porphyrin

tumor cells

M. Graca, H. Vicente, “Syntheses of carbon-carbon linked carboranylated porphyrins for boron neutron capture therapy of cancer,” Tetrahydron letters. 41, 7623-7627 (2000(.

A. H. Soloway, W. Tjanks, B. A. Barnum, “The chemistry of neutron capture therapy,” Chem. Rev. 98, 1515-1562 (1998).

R. J. Fiel, E. Mark, “Mechanism of the localization of manganese(III) Meso-Tetra(4-Sulfonatophenyl) porphyrine in mice bearing L1210 tumors,” Cancer Letters, 40, 23-32 (1998).

F. Megnin, P. J. Faustino, “Studies on the mechanism of selective retention of porphyrins and metalloporphyrins by cancer cells,” Biochimica et Biophysica Acta, 929, 173-181 (1978).

J. L. Sessler and R. A. Miller, “Texaphyrins; New drugs with diverse clinical application in radiation and photodynamic Therapy,” Biochemical Pharmacology. 59, 733-734 (2000).

E. P. Kyba, R. E. Davis, C. W. Hudson, A. M. John, S. B. Brown, L. K. Mephaul. A. C. Glover, “Tetradentate 14-membered tetra-phosphino-containing macrocycles,” J. Am. Chem. Soc, 103, 3868-3875 (1981).

J. L. Sessler, V. Lynch, M. R. Johnson, “Synthesis and Crystal Structure of a novel Tripyrran-Containing Porphyrinogen-like macrocycle,” J. Org. Chem. 52, 4394-4397 (1987).

J. L. Sessler, G. Hemmi, T. D. Mody, T. Murai, A. Burreil, S. W. young, “Texaphyrins: Synthesis and Applications,” Acc. Chem. Res. 27, 43-50 (1994).

P. S. Clezy, C. Y. Fookes, J. A. Liepa, “The chemistry of pyrrolic compounds,”Aust. J. Chem. 25, 1979-1990 (1972).

C. P. Wong, “[5, 10, 15, 20-Tetraphenylporphyrinato (2-)] Lantanides and [5, 10, 15, 20- Tetraphenylporphyrinato(2-)] Actinides,” Inorg. Syn. 22, 156-162 (1983).

J. L. Sessler, T. Murai, G. Hemmi, “A water-stable Gd(III) complex derived from a new pentadentate expanded porphyrin ligand. Inorg. ,” Chem. 28, 3390-3393 (1989).
S. W. Young, K. W. Woodburn, M. Wright, “Lutetium Texaphyrin (PCI-0123): A near-infrared, water-soluble photosensitizer,” Photochemistry and Photbiology, 63(6), 892-897, (1996).
J. L. sessler, N. A. Tvermoes, D. G. Guldi, T. D. Mody, W. E. Allen, “One-electron reduction and oxidation sensitizer Gd(III) Texaphyrin (PCI-0120) and other water soluble metallotexaphyrins,” J. Phys. Chem. A. 103, 787-794, (1999).
F. Alanazi, H. Li, S. Oie, D. R. Lu, “Synthesis of carborane mimics of cholestrol ester and studies of there liposomsl formulations for targeted drug delivery,” J. Pharm. Sci. (2002), (Submit).
J. L. Sessler, W. E. Allen, V. A. Kral, “Highly boronated derivatives of texaphyrins,” US. Patent 5955586 (1999).
Ninth International Symposium on Neutron Capture Therapy for cancer, Osaka International Convention Center, Osaka, Japan, 334P, October 2-6 (2000).
J. L. Sessler and R. A. Miller, “Biochem. Pharm. texaphyrins; new drugs with diverse clinical application in radiation and photodynamic therapy,” Biochem. Pharm. 59, 733-739 (2000).
J. L. Sessler and T. Murai, “An expanded porphyrin: the synthesis and structure of a new aromatic pentadentate ligand,” J. Am. Chem. Soc. 110, 5586-5588 (1988).
D. Magda, C. Lee, J. Sessler, “Redox cycling by motexafin gadolinium enhances cellular response to ionizing radiation by forming reactive oxygen species,” Int. J. Radiat. Oncol. Biol. Phys. 51, No. 4, 1025-1036 (2001).
S. Xu and K. Zakian, “Effect of motexafin Gd on tumor metabolism and radiation sensivity,” Int. J. Rad. Onc. Biol. Phys. 49, No. 5, 1381-1390 (2001).
J. L. Sessler, T. D. Mody, “Gd(III) Texaphyrin: A novel MRI contrast agent,” J. Am. Chem. Soc. 115, 10368-10369 (1993).
D. I. Rosenthal and P.Nurenberg, “A phase I single-dose trial of Gd-Tex, a tumor selective radiation sensitizer detectible by MRI,” Clinical Cancer Res. 5, 739-745 (1999).