The Chemistry of Neutron Capture Therapy

Ah, Soloway; Tjarks, Werner; Ba, Barnum; Fg, Rong; Rf, Barth; Im, Codogni; Jg, Wilson

doi:10.1021/cr941195u

Cited by 1,144 publications

(778 citation statements)

References 402 publications

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“…Boron-containing polyhedral compounds have been intensively studied because of their use in boron neutron capture therapy (12) and in radioimaging (13,14). From the structural point of view, the variety of known structural types of boranes, heteroboranes, and metallaboranes represents an interesting counterpart to organic compounds, especially to aromates.…”

mentioning

confidence: 99%

From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease

Cígler

Kožíšek

Řezáčová

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

292

273

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HIV protease (PR) represents a prime target for rational drug design, and protease inhibitors (PI) are powerful antiviral drugs. Most of the current PIs are pseudopeptide compounds with limited bioavailability and stability, and their use is compromised by high costs, side effects, and development of resistant strains. In our search for novel PI structures, we have identified a group of inorganic compounds, icosahedral metallacarboranes, as candidates for a novel class of nonpeptidic PIs. Here, we report the potent, specific, and selective competitive inhibition of HIV PR by substituted metallacarboranes. The most active compound, sodium hydrogen butylimino bis-8,8-[5-(3-oxa-pentoxy)-3-cobalt bis(1,2-dicarbollide)]di-ate, exhibited a Ki value of 2.2 nM and a submicromolar EC50 in antiviral tests, showed no toxicity in tissue culture, weakly inhibited human cathepsin D and pepsin, and was inactive against trypsin, papain, and amylase. The structure of the parent cobalt bis(1,2-dicarbollide) in complex with HIV PR was determined at 2.15 Å resolution by protein crystallography and represents the first carborane-protein complex structure determined. It shows the following mode of PR inhibition: two molecules of the parent compound bind to the hydrophobic pockets in the flap-proximal region of the S3 and S3 subsites of PR. We suggest, therefore, that these compounds block flap closure in addition to filling the corresponding binding pockets as conventional PIs. This type of binding and inhibition, chemical and biological stability, low toxicity, and the possibility to introduce various modifications make boron clusters attractive pharmacophores for potent and specific enzyme inhibition. rational drug design ͉ aspartic proteases ͉ carboranes ͉ x-ray structure analysis ͉ virostatics

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mentioning

confidence: 99%

From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease

Cígler

Kožíšek

Řezáčová

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

292

273

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“…Recently, new generations of boron compounds have been designed to achieve higher tumor cell selectivity than the previous BNCT agents. Boron containing amino acids, related peptides, porphyrins, DNA binders, and other tumor-targeting anchor agents are being attached to a polyhedral borane skeleton for better tumor-cell recognition (75,76).…”

Section: Clusters In Biology and Medicinementioning

confidence: 99%

Clusters: A bridge across the disciplines of environment, materials science, and biology

Castleman

Jena

2006

Proc. Natl. Acad. Sci. U.S.A.

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“…Application of boron compounds selectively accumulated in tumor allows us to provide the lethal effect after the capture reaction, primarily in tumor cells. Currently, two compounds are used in the clinical practice of the boron neutron capture therapy (BNCT): p-boronophenylalanine (BPA) and mercaptododecaborate sodium (Na 2 B 12 H 11 SH), but these compounds are not ideal for BNCT and therefore studies of new and more effective boron compounds is conducted [2][3][4].…”

Section: Introductionmentioning

confidence: 99%

The study of hyaluronic acid compounds for neutron capture and photon activation therapies

et al. 2014

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Abstract:The therapy of radioresistant tumors remains an urgent problem in medicine. To solve this problem neutron capture therapy (NCT) and photon activation therapy (PAT) are used. The essential feature of this such technique is the uptake of tumor chemical elements, which interact with thermal neutrons (NCT) and X-rays (PAT). The aims of the investigation were to study a biodistribution of the complexes of hyaluronic acid with boron (3 mg B mL -1 ) and gold (20 mg Au mL -1 ) in mice with melanoma B-16 after intratumoral administration. An optimal time for NCT was 30 minutes after administration when boron concentration in the tumor was more than 30 µg g -1 and exceeded boron content in surrounding tissues. The maximal gold content in tumor (180-260 mg g -1 ) was obtained in 30 minutes after the preparation introduction. The highest ratios of gold in tumor and surrounding tissues (a necessary condition for forming of the local absorbed dose in tumor) was obtained in 0.5 and 1 h. On the basis of the data obtained, it is possible to assume the perspectives of the non-toxic boron compounds for use in NCT and the gold compounds for use primarily as contrast agents for diagnostic purposes.

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The Chemistry of Neutron Capture Therapy

Cited by 1,144 publications

References 402 publications

From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease

From nonpeptide toward noncarbon protease inhibitors: Metallacarboranes as specific and potent inhibitors of HIV protease

Clusters: A bridge across the disciplines of environment, materials science, and biology

The study of hyaluronic acid compounds for neutron capture and photon activation therapies

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