BNCT Agents Research Articles

Synthesis of Functionalized Carboranes as Potential Anticancer and BNCT Agents

Carboranyl aldehydes react with alpha,beta-unsaturated esters, ketones, and nitriles in the presence of DABCO to provide functionalized carboranyl alcohols in good yields. Acetates of these alcohols undergo a facile isomerization with a variety of nucleophiles and afford structurally interesting carboranes. Biological evaluation of these molecules exhibited impressive antiproliferative activity for brain and breast cancer cells.

Synthesis of tetrasubstituted Zn(II)-phthalocyanines carrying four carboranyl-units as potential BNCT and PDT agents

The synthesis of two tetrasubstituted zinc(II)phthalocyanines carrying four carbon–carbon linked o-carboranyl-units (40 boron atoms, 27.5% boron by weight) is presented. In an in vitro model test the new compounds showed a good photosensitizing efficiency, that encourages further studies for their evaluation as possible BNCT–PDT sensitizers.

Synthesis of mono- and bisglucuronylated carboranes

A route for the preparation of carborane-containing glucuronic acid derivatives is described, starting from 1,2- O-isopropylidene-α- d-glucuronolactone. The obtained compounds are potential BNCT agents ready to be tested for their uptake in selected tumor cell lines.

Synthesis of Novel Carborane-hybrids Based on a Triazine Scaffold for Boron Neutron Capture Therapy

Cyanuric chloride has been used as a scaffold for the synthesis of potential agents for BNCT containing a carborane cluster, a sugar moiety as hydrophilic arm and an amino acid for the con­jugation with bioactive molecules; this approach is, in principle, particularly suitable for a combinatorial approach.

Synthesis of homoleptic Re(I) complexes of isocyano-carboranes and the X-ray structure of hexakis( p-carboran-1-yl-isonitrile)Re(I)

Two homoleptic Re(I) complexes of ortho and para-carborane isocyanide ligands were prepared as the first examples of a new class of metal-based BNCT and BNCS agents. The target compounds were prepared in low yield through the reaction of [Re 2(O 2CPh) 4Cl 2] and [Re 2(OAc) 4Cl 2] with 3-isocyano-1,2-dicarba- closo-dodecaborane and a para-carborane azetidine derivative respectively. The desired product from the latter reaction was characterized crystallographically and is only the second reported molecular structure of a homoleptic Re(I) isonitrile complex.

Linkage of boronated polylysine to glycoside moieties of polyclonal antibody; boronated antibodies as potential delivery agents for neutron capture therapy

Among the ways to deliver comparatively large amounts of boron to cells in vitro for boron neutron capture studies is the linkage of a boronated macromolecule such as polylysine to an antibody. In order to reduce interference with immunoreactivity, boronated polylysine (BPL) was linked to oligosaccharide moieties on the IgG molecule distant from the antibody combining sites. The resultant bioconjugate was chromatographically separated from free BPL and unconjugated antibody using a Sephacryl S300 column. The total measured boron per BPL-IgG conjugate, determined by direct current plasma atomic emission spectroscopy, was estimated to be ∼6 × 103 atoms. This, together with molecular weight estimations, indicated conjugation of about 3 polylysines to each IgG molecule. Immunoreactivity of the conjugate was found to be the same as that of the unconjugated polyclonal antibody. This was based on its concentration dependent interference with immunometric reactions for an antigen (TSH), whereas heat inactivated or non-specific antibody had no such inhibitory effects. The results support the hypothesis that the binding affinity of the conjugate for antigen was preserved after its linkage to BPL under the conditions described. The methodology described in this report may have applicability for the preparation of boronated antibodies as delivery agents for BNCT.

ChemInform Abstract: Synthesis of O‐Bonded Derivatives of closo‐Dodecaborate Anion. [B12]‐[C2B10] Double Cage Boron Compounds ‐ A New Approach to Synthesis of BNCT Agents

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of carboranyl derivatives of alkynyl glycosides as potential BNCT agents

A series of amphiphilic carbohydrate-carborane hybrids consisting of a lipophilic core (carborane cage) and a glycoside moiety for conferring high-affinity recognition by the cellular lectins have been prepared in a chemically accessible fashion.

Synthesis of boron-containing cholesterol derivatives for incorporation into unilamellar liposomes and evaluation as potential agents for BNCT

Four carborane-containing derivatives of cholesterol were prepared for incorporation into the bilayer of unilamellar liposomes and evaluation as potential agents for boron neutron capture therapy. The derivatives enable the evaluation of the linker moiety and the type of carborane head group on the bilayer stability and ultimate in vivo tumor specificity.

ChemInform Abstract: Synthesis of a New Amphiphilic ortho‐Carborane as a Potential BNCT Agent: 4‐[N,N‐Formyl‐(ortho‐carboranylmethyl)amino]benzoyl‐L‐glutamic Acid.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of a new amphiphilic ortho-carborane as a potential BNCT agent: 4-[N,N-formyl-(ortho-carboranylmethyl)-amino]benzoyl-L-glutamic acid

A 1,2-dicarba-closo-dodecaboranyl derivative (8) and its disodium salt (9) were prepared from 4-aminobenzoic acid (1). The water solubility and the biological data (toxicity and cell-uptake) of the disodium salt (9) were identified to be enough for clinical trial.

Synthesis of alkoxy derivatives of dodecahydro- closo-dodecaborate anion [B 12H 12] 2−

Dodecahydro- closo-dodecaborate anion [B 12H 12] 2− is a stable non-toxic highly water-soluble boron-rich compound. Functionalized derivatives of this compound are of high interest as BNCT agents. There are however very few routes for the functionalizing of the cage. The present contribution describes a way to overcome this problem and to attach [B 12H 12] 2− to organic molecules including biomolecules. A number of alkoxy derivatives of dodecahydro- closo-dodecaborate anion [B 12H 11OR] 2− (R = Et, i-Pr, C 16H 33, allyl, benzyl, p-CH 2C 6H 4CN, p-CH 2C 6H 4NO 2, p-CH 2CH 2C 6H 4NO 2, and CH 2CH 2N(CO) 2C 6H 4) were prepared by the reaction of (Bu 4N) 2[B 12H 11OH] with the corresponding alkyl bromides or iodides in acetone in the presence of K 2CO 3. This route can be used for synthesis of water-soluble derivatives of the dodecahydro- closo-dodecaborate anion for potential use in Boron Neutron Capture Therapy. [Display omitted]

Synthesis and biological evaluation of boron-containing polyamines as potential agents for neutron capture therapy of brain tumors.

New boron-containing spermidine/spermine (SPD/SPM) analogues have been synthesized: N5-[4-(2-aminoethyl-o-carboranyl)butyl] and N5-{4-[(2,3-dihydroxypropyl)-o-carboranyl]butyl} SPD/SPM derivatives (ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5) as well as N5-{[4-(dihydroxyboryl)phenyl]methyl}spermidine (BBSPD-5). These boronated polyamines retain their ability to displace ethidium bromide from calf thymus DNA and are rapidly taken up in vitro by F98 rat glioma cells. The in vitro toxicities of ASPD-5, ASPM-5, DHSPD-5, and DHSPM-5 are lower than those previously reported for N5-[4-(o-carboranyl)butyl] SPD/SPM derivatives (SPD-5 and SPM-5) but similar to those of native SPD and SPM. Very low toxicity was also observed for BBSPD-5. In vivo studies of ASPD-5 and BBSPD-5 were performed in mice bearing intracerebral implants of the GL261 glioma and subcutaneous implants of the B16 melanoma. The biodistribution data found in both tumor models suggest that the polyamines synthesized to date do not appear to be suitable boron agents for BNCT.

ChemInform Abstract: Synthesis of Novel Boronated Acridines and Spermidines as Possible Agents for BNCT.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of novel boronated acridines- and spermidines as possible agents for BNCT

An approach to synthesise three different boronated DNA-interacting compounds ( 11, 15 & 19) is described. Compound 11 is containing both an acridine system and a spermidine residue. The acridine moiety would serve as DNA-intercalating fragment whereas the spermidine residue functions both as water-solubilising and DNA-interacting part. 1,12- p-Carboranyl bis[( N-3-aminopropyl, N-4-aminobutyl)-3-propane amide] hydrogen chloride ( 15) was obtained by treating 13 first with ethyl chloroformate and then the secondary amine 2. Finally, 1,12-Bis( N-(9-acridinyl)3-aminopropyl)- p-carborane hydrogen chloride ( 19) was accomplished by hydrochloronation of the corresponding free amine which was obtained by the treatment of 18 with 9 in toluene/DMF.

ChemInform Abstract: Synthesis and Biochemical Activity of Hydrophilic Carborane‐Containing Pyrimidine Nucleosides as Potential Agents for DNA Incorporation and BNCT.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of 1-Amino-3-[2-(1,7-dicarba-closo-dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic Acid: A Potential BNCT Agent.

The synthesis of an unnatural amino acid, 1-amino-3-[2-(1,7-dicarba-closo-dodecaboran(12)-1-yl)ethyl]cyclobutanecarboxylic acid, was achieved. This new potential BNCT agent was prepared via the monoalkylation of m-carborane with 4-bromobutene to produce 4-m-carboranyl-1-butene, which was then subjected to a 2 + 2 cycloaddition using dichloroketene. The resultant boronated cyclobutanone was reductively dechlorinated prior to the formation of the corresponding hydantoin, which was hydrolized to the title compound in excellent yield.

Synthesis and Biochemical Activity of Hydrophilic Carborane-Containing Pyrimidine Nucleosides as Potential Agents for DNA Incorporation and BNCT

A novel type of hydrophilic 5-tethered carborane-containing 2′-deoxyuridine derivative, SUB-7-DIOL, has been developed. This compound is a potential agent for DNA incorporation and BNCT, because it showed satisfactory aqueous solubility and demonstrated an excellent rate of phosphorylation by human thymidine kinase. This study also demonstrated the importance of tethering a flexible hydrocarbon chain between the carborane cage and the 5-position of the nucleoside, and the effectiveness of a water-solubilizing moiety attached to the carbon atom of the lipophilic carborane cage.

Synthesis of carboranyl polyamines for DNA targeting

Three groups of internal and terminal N-substituted carboranyl spermidines spermines were synthesized as potential BNCT agents for the treatment of malignant tumors.

A method for imaging nuclei with short T2 relaxation and its application to boron-11 NMR imaging of a BNCT agent in an intact rat

A method for imaging nuclei with short T2 relaxation and its application to boron-11 NMR imaging of a BNCT agent in an intact rat