Synthesis of a porphyrin-labelled carboranyl phosphate diester: a potential new drug for boron neutron capture therapy of cancer

Maderna, Andreas; Huertas, Ramon; Hawthorne, M. Frederick; Luguya, Raymond; Vicente, M. Graça H.

doi:10.1039/b203730k

Cited by 34 publications

(12 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…13 -18,24 We recently reported the condensation of porphyrin 6 with a dimeric carboranyl phosphate diester via an amide linkage, to give a negatively-charged conjugate, which is currently being evaluated in our laboratories as a boron delivery agent for BNCT. 16 Alkylation of aminoporphyrins 7 and 8 with methyl iodide in the presence of a bulky base produced two positively charged porphyrins, DADP-o and DADP-a, with potential application in PDT. 11 Reductive amination 25 of 1-formyl-ocarborane using tri-aminoporphyrin 9, leads to a tricarboranylporphyrin with potential application in BNCT (Scheme 1).…”

Section: Resultsmentioning

confidence: 99%

“…12 Therefore, nitro-and amino-substituted amphiphilic porphyrins are useful synthetic precursors to biologically active molecules. Furthermore, nitro and amino groups can be easily functionalized, 11,13,14 and conjugated with bioactive molecules, such as monoclonal antibodies, 15 oligomeric carboranyl phosphate diesters, 16 polymer backbones, 17 and cyclodextrins. 18 Current synthetic routes to mono-, di-and tri-nitro functionalized meso-tetraphenylporphyrins involve total synthesis via a crossed Rothemund approach, 17 or by electrophilic nitration of the p-phenyl groups of mesotetraphenylporphyrin (TPP, 1).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Synthesis and reactions of meso-(p-nitrophenyl)porphyrins

et al. 2004

Self Cite

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and reactions of meso-(p-nitrophenyl)porphyrins

et al. 2004

Self Cite

View full text Add to dashboard Cite

“…Despite their multiple negative charges, oligomeric phosphate diesters have been shown to target the nuclei of TC7 cells following microinjection (69), suggesting that the combination of oligomeric phosphate diesters with a celltargeting molecule capable of crossing the plasma membrane could provide both selectivity and nuclear binding. Such a conjugate recently has been designed and synthesized (70), although its biological evaluation has yet to be reported.…”

Section: Low Molecular Weight Agentsmentioning

confidence: 99%

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Barth

Coderre²,

Vicente³

et al. 2005

Clinical Cancer Research

895

666

View full text Add to dashboard Cite

Background: Boron neutron capture therapy (BNCT) is based on the nuclear reaction that occurs when boron-10 is irradiated with low-energy thermal neutrons to yield high linear energy transfer A particles and recoiling lithium-7 nuclei. Clinical interest in BNCT has focused primarily on the treatment of high-grade gliomas and either cutaneous primaries or cerebral metastases of melanoma, most recently, head and neck and liver cancer. Neutron sources for BNCT currently are limited to nuclear reactors and these are available in the United States, Japan, several European countries, and Argentina. Accelerators also can be used to produce epithermal neutrons and these are being developed in several countries, but none are currently being used for BNCT. Boron Delivery Agents: Two boron drugs have been used clinically, sodium borocaptate (Na 2 B 12 H 11 SH) and a dihydroxyboryl derivative of phenylalanine called boronophenylalanine. The major challenge in the development of boron delivery agents has been the requirement for selective tumor targeting to achieve boron concentrations (f20 Ag/g tumor) sufficient to deliver therapeutic doses of radiation to the tumor with minimal normal tissue toxicity. Over the past 20 years, other classes of boron-containing compounds have been designed and synthesized that include boroncontaining amino acids, biochemical precursors of nucleic acids, DNA-binding molecules, and porphyrin derivatives. High molecular weight delivery agents include monoclonal antibodies and their fragments, which can recognize a tumor-associated epitope, such as epidermal growth factor, and liposomes. However, it is unlikely that any single agent will target all or even most of the tumor cells, and most likely, combinations of agents will be required and their delivery will have to be optimized. Clinical Trials: Current or recently completed clinical trials have been carried out inJapan, Europe, and the United States. The vast majority of patients have had high-grade gliomas. Treatment has consisted first of ''debulking'' surgery to remove as much of the tumor as possible, followed by BNCTat varying times after surgery. Sodium borocaptate and boronophenylalanine administered i.v have been used as the boron delivery agents. The best survival data from these studies are at least comparable with those obtained by current standard therapy for glioblastoma multiforme, and the safety of the procedure has been established. Conclusions: Critical issues that must be addressed include the need for more selective and effective boron delivery agents, the development of methods to provide semiquantitative estimates of tumor boron content before treatment, improvements in clinical implementation of BNCT, and a need for randomized clinical trials with an unequivocal demonstration of therapeutic efficacy. If these issues are adequately addressed, then BNCTcould move forward as a treatment modality.

show abstract

“…In addition to their application in photodynamic therapy as a photosensitizer, porphyrins have been conjugated to boronrich moieties for BNCT applications [64]. One such porphyrin, tetra-(4-nido-carboranylphenyl) porphyrin (H 2 TCP), contains 36 boron atoms per molecule (Fig.…”

Section: Porphyrinsmentioning

confidence: 99%

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

2015

View full text Add to dashboard Cite

Boron neutron capture therapy (BNCT) is a promising cancer therapy modality that utilizes the nuclear capture reaction of epithermal neutrons by boron-10 resulting in a localized nuclear fission reaction and subsequent cell death. Since cellular destruction is limited to approximately the diameter of a single cell, primarily only cells in the neutron field with significant boron accumulation will be damaged. However, the emergence of BNCT as a prominent therapy has in large part been hindered by a paucity of tumor selective boron containing agents. While L-boronophenylalanine and sodium borocaptate are the most commonly investigated clinical agents, new agents are desperately needed due to their suboptimal tumor selectivity. This review will highlight the various strategies to improve tumor boron delivery including: nucleoside and carbohydrate analogs, unnatural amino acids, porphyrins, antibody-dendrimer conjugates, cationic polymers, cell-membrane penetrating peptides, liposomes and nanoparticles.

show abstract

Synthesis of a porphyrin-labelled carboranyl phosphate diester: a potential new drug for boron neutron capture therapy of cancer

Abstract: A boron-rich, water-soluble porphyrin conjugate was synthesized by coupling of two carboranyl alcohols with 2-chlorophenoxyphosphorus dichloride, followed by conjugation to an amine-functionalized tetraphenyl-porphyrin via an amide linkage.

Cited by 34 publications

References 16 publications

Synthesis and reactions of meso-(p-nitrophenyl)porphyrins

Synthesis and reactions of meso-(p-nitrophenyl)porphyrins

Boron Neutron Capture Therapy of Cancer: Current Status and Future Prospects

Advancements in Tumor Targeting Strategies for Boron Neutron Capture Therapy

Contact Info

Product

Resources

About