Chemistry and Pharmacology of Agents for BNCT

Feakes, Debra A.

doi:10.1007/978-1-4615-1285-1_3

Cited by 2 publications

(4 citation statements)

References 16 publications

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“…The 10 boron neutron-capture therapy (BNCT) of cancer has attracted increasing biomedical interest (Feakes, 2001;Wittig et al, 2008a;Barth, 2009;Hopewell et al, 2011;Schwint and Trivillin, 2015;Farhood et al, 2018;Fukuda, 2021;Sauerwein et al, 2021). According to the nuclear equation: 10 B + 1 n → 4 He + 7 Li + γ, the process requires a stable 10 B-containing agent that accumulates selectively in the tumor, which is then irradiated with slow, low-energy thermal neutrons.…”

Section: Introductionmentioning

confidence: 99%

“…The most employed 10 B-containing agents, and the only ones approved for use in humans, are 4-borono-phenylalanine (BPA), and the boron clusters decahydro-decaborate (GB-10) and [Na 2 B 12 H 11 SH] 2-(BSH) (Feakes, 2001;Schwint and Trivillin, 2015;Schwint et al, 2020;Sauerwein et al, 2021). As natural boron contains ~81% of 11 B and only ~19% of 10 B, boron-containing agents must be enriched in 10 B to >98% for BNCT (Pozzi et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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In vivo polymerization of the dopamine-borate melanin precursor: A proof-of-concept regarding boron neutron-capture therapy for melanoma

Stockert¹,

ROMERO²,

Felix-Pozzi³

et al. 2023

Biocell

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The 10 boron neutron-capture therapy (BNCT) is an emerging antitumoral method that shows increasing biomedical interest. BNCT is based on the selective accumulation of the 10 boron isotope within the tumor, which is then irradiated with low-energy thermal neutrons, generating nuclear fission that produces 7 lithium, 4 helium, and γ rays. Simple catechol-borate esters have been rather overlooked as precursors of melanin biosynthesis, and therefore, a proof-of-concept approach for using dopamine-borate (DABO) as a suitable boron-containing candidate for potential BNCT is presented here. DABO can spontaneously oxidize and autopolymerize in vitro, giving a soluble, eumelaninlike brown-black poly-DABO product. Melanotic melanoma cell cultures treated with 1 mM DABO for 24 and 48 h were viable and showed no signs of damage or cell death. The stability and possible trans-esterification of DABO is shortly discussed. Chemical calculations and quantitative structure-activity relationships (QSAR) analysis of DABO and the BNCT agent BPA indicated that they should be cell permeant and accumulate within lysosomes and melanosomes. Molecular modeling allows visualization of both the DABO precursor and the structure of a borate derivative of the proposed catechol-porphycene model for eumelanin, showing interesting features from molecular orbital calculations. The main difference between DABO and other agents, such as BPA, is that it is not a boronic acid nor a boron cluster. This simple catechol-borate ester (protected from oxidation and blackening) could be administrated to living cells and organisms, in which biosynthesis of boron-melanin in melanoma melanocytes can lead to improved BNCT.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

In vivo polymerization of the dopamine-borate melanin precursor: A proof-of-concept regarding boron neutron-capture therapy for melanoma

Stockert¹,

ROMERO²,

Felix-Pozzi³

et al. 2023

Biocell

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“…The 10 boron neutron-capture therapy (BNCT) of cancer is a novel therapeutic modality that counts with an increasing biomedical potential and many interesting applications [1][2][3][4][5][6][7][8]. BNCT requires a 10 B-containing agent that accumulates selectively in the tumor, which is then subjected to irradiation with lowenergy thermal neutrons.…”

Section: Introductionmentioning

confidence: 99%

“…So, the chemistry of boroncontaining metabolites and boron clusters has been reviewed [9,10,11]. 10 B-containing agents are mainly BPA (4-boronophenylalanine), and deca-or dodeca-clusters of B atoms such as GB-10 and BSH [1,5,8,12], which are the only ones approved for use in Oncology, especially for BNCT of skin melanomas [13][14][15][16][17][18]. As an amino acid analogue, non-specific binding of BPA to proteins of cells and tissues are expected to occur.…”

Section: Introductionmentioning

confidence: 99%

Molecular Modeling of Phenyl-Boronic Acids and Catechol-Borate Esters: A Mechanistic Rationale for Boron Binding to Melanin Catechols, Regarding the 10Boron Neutron-Capture Therapy of Melanoma

Stockert

2022

ARR

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The 10 boron neutron-capture therapy (BNCT) is an emerging anti-tumor therapy based on the accumulation of a 10 B isotope within the tumor followed by irradiation with low-energy neutrons. The nuclear fission process produces 7 lithium, 4 helium, and λ rays within the tumor tissue, inducing specific tumor cell damage and death. 10 B can be delivered either as simple B-containing agents or as B clusters. In the first case, boronic acid derivatives such as 4-borono-phenylalanine (BPA) are currently applied for BNCT of melanoma and other tumors. Although it can be assumed that BPA would act as a precursor metabolite for melanin biosynthesis, the precise action mechanism is not yet clear. Direct binding of this boronic acid to a target substrate, namely the catechol groups from already synthesized melanin, could be an alternative mechanism. In keeping with this, high affinity for melanin would explain the action mode of boronic acids as melanoma seekers. DOPA-and dopamine-borate esters are also potential B-carrier candidates for BNCT, and they could be incorporated as melanin precursors or binding reagents. In this work, molecular modeling methods have been applied to analyze the structure of boronic acid and borate ester derivatives, as well as their interaction and binding mode with the recently proposed catechol-porphycene model for the melanin polymer. Interestingly, remarkable structural features drawn from chemical geometry, and also molecular orbital calculations, support the possibility that boronic acids and borate esters could be reactive agents for direct binding to melanin catechols.

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Chemistry and Pharmacology of Agents for BNCT

Cited by 2 publications

References 16 publications

In vivo polymerization of the dopamine-borate melanin precursor: A proof-of-concept regarding boron neutron-capture therapy for melanoma

In vivo polymerization of the dopamine-borate melanin precursor: A proof-of-concept regarding boron neutron-capture therapy for melanoma

Molecular Modeling of Phenyl-Boronic Acids and Catechol-Borate Esters: A Mechanistic Rationale for Boron Binding to Melanin Catechols, Regarding the 10Boron Neutron-Capture Therapy of Melanoma

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