Boronated DNA-Binding Compounds as Potential Agents for Boron Neutron Capture Therapy

Abstract

Boron Neutron Capture Therapy (BNCT) is a binary cancer treatment that exploits the short range particles released from a nuclear fission reaction involving the non-radioactive 10B nucleus and low-energy (thermal) neutrons for the destruction of tumour cells. If boronated agents are targeted towards chromosomal DNA, the efficiency of BNCT is greatly enhanced. This article presents a concise review of DNA-binding compounds that have been functionalised with boron.

Synthesis, characterization and biological evaluation of carboranylmethylbenzo[b]acridones as novel agents for boron neutron capture therapy

“…1.4 × 10 11 B atoms and consequently 2.8 × 10 10 10 B atoms per cell, an amount superior to the recommended concentration of 10 8 -10 9 10 B atoms. 25 …”

“…[18][19][20][21][22] DNA binding agents and tumour seeking molecules like porphyrins and porphyrinic macrocyclic compounds, such as phthalocyanines, are also alternatives for selective delivery of the boron moiety into tumour cells. [23][24][25][26][27] However, until now there has been no new boron compound that has reached the stage for phase I clinical trials. Both BSH and BPA still remain today as the only two drugs in clinical trials for BNCT.…”

A theranostic approach based on the use of a dual boron/Gd agent to improve the efficacy of Boron Neutron Capture Therapy in the lung cancer treatment

“…Currently, two BNCT drugs are available for clinical investigation namely: i)Lpara-boronophenylalanine (BPA), structurally related to the amino acid phenylalanine, that has been used in clinical trials to treat glioblastoma, head and neck recurrent cancer and melanoma 7 and ii) sodium mercaptoundecahydro-closo-dodecaborate (BSH) that has been investigated for the . Carboranes are icosahedral cages containing 10 boron atoms and they have been used to design boron delivery vehicles due to their high boron content, chemical versatility and in vivo stability [10][11] . Carborane based agents may be functionalized with small targeting moieties including amino acids, vitamins, carbohydrates, porphyrinates, ect.…”

Uptake and Distribution of a Platinum(II)-Carborane Complex Within a Tumour Cell Using Synchrotron XRF Imaging

“…Their interaction results in a localized nuclear fission reaction that is capable of destroying malignant cells into which 10 B agents have been incorporated. [1,2] The selective delivery of 10 B to critical cell components, in particular chromosomal DNA, greatly enhances the effectiveness of the neutron capture reaction and the delivery of boron to this important biomolecule is an area of great interest. [2] The interactions of Pt complexes with DNA, including covalent binders such as cisplatin and its analogues and DNA metallointercalators such as those based upon the Pt II -terpy (terpy ¼ 2,2 0 :6 0 ,2 00 -terpyridine) framework, have been studied in great detail over the past few decades.…”

“…[1,2] The selective delivery of 10 B to critical cell components, in particular chromosomal DNA, greatly enhances the effectiveness of the neutron capture reaction and the delivery of boron to this important biomolecule is an area of great interest. [2] The interactions of Pt complexes with DNA, including covalent binders such as cisplatin and its analogues and DNA metallointercalators such as those based upon the Pt II -terpy (terpy ¼ 2,2 0 :6 0 ,2 00 -terpyridine) framework, have been studied in great detail over the past few decades. [3][4][5][6][7][8][9] More recently, highly sensitive analytical techniques such as synchrotron X-ray fluorescence (XRF) have emerged as viable methods for the imaging of very low levels of individual elements within biological samples including whole cells.…”