RESUMEN
Boron neutron capture therapy (BNCT) is one of the most promising treatments among neutron capture therapies due to its long-term clinical application and unequivocally obtained success during clinical trials. Boron drug and neutron play an equivalent crucial role in BNCT. Nevertheless, current clinically used l-boronophenylalanine (BPA) and sodium borocaptate (BSH) suffer from large uptake dose and low blood to tumor selectivity, and that initiated overwhelm screening of next generation of BNCT agents. Various boron agents, such as small molecules and macro/nano-vehicles, have been explored with better success. In this featured article, different types of agents are rationally analyzed and compared, and the feasible targets are shared to present a perspective view for the future of BNCT in cancer treatment. This review aims at summarizing the current knowledge of a variety of boron compounds, reported recently, for the application of BCNT.
Asunto(s)
Terapia por Captura de Neutrón de Boro , Neoplasias , Humanos , Boro/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/radioterapia , Compuestos de Boro/uso terapéuticoRESUMEN
Boron neutron capture therapy (BNCT) is a potential radiation therapy modality for cancer, and tumor-targeted stable boron-10 (10B) delivery agents are an important component of BNCT. Currently, two low-molecular-weight boron-containing compounds, sodium mercaptoundecahydro-closo-dodecaborate (BSH) and boronophenylalanine (BPA), are mainly used in BNCT. Although both have suboptimal tumor selectivity, they have shown some therapeutic benefit in patients with high-grade glioma and several other tumors. To improve the efficacy of BNCT, great efforts have been devoted for the development of new boron delivery agents with better uptake and favorable pharmacokinetic profiles. This article reviews the application and research progress of boron nanomaterials as boron carriers in boron neutron capture therapy and hopes to stimulate people's interest in nanomaterial-based delivery agents by summarizing various kinds of boron nanomaterial patents disclosed in the past decade.
RESUMEN
Boron nanoparticles (BNPs), functionalized with hydroxyl groups, were synthesized in situ by a cascade process, followed by bromination and hydrolyzation reactions. These functionalized BNPs, (B m (OH) n ), were characterized using 1H and 11B NMR spectra, Fourier-transform infrared (FT-IR) spectroscopy, inductively coupled plasma-optical emission spectroscopy (ICP-OES), transmission electron microscopy (TEM), dynamic light scattering (DLS), and X-ray photoelectron spectroscopy (XPS) methods. These nanoparticles were also evaluated in vitro for their antimalarial activity against Plasmodium falciparum (3D7 strain) with an IC50 value of 0.0021 µM and showed low toxicity to Uppsala 87 malignant glioma (U87MG) cell lines, malignant melanoma A375 cell lines, KB human oral cancer cell lines, rat cortical neuron cell lines, and rat fibroblast-like synoviocyte (FLS) cell lines.
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Carboxyboranylamino ethanol (Me2N(BH2CO2H)CH2CH2OH, 1) was prepared in 75.0% yield by an amine-exchange reaction. Compound 1 shows lower cytotoxicity and higher anti-tumor efficacy in vitro towards the SCCVII cell line in comparison with 4-borono-L-phenylalanine (BPA) and methyl 2-hydroxyl-5-(1'-ortho-carbonylmethyl-1',2',3'-triazol-4'-yl)-benzonate (2). The bio-enhancement is interpreted using molecular docking calculations.
Asunto(s)
Amino Alcoholes/farmacología , Antineoplásicos/farmacología , Compuestos de Boro/farmacología , Terapia por Captura de Neutrón de Boro , Carcinoma de Células Escamosas/tratamiento farmacológico , Descubrimiento de Drogas , Amino Alcoholes/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Compuestos de Boro/química , Línea Celular Tumoral , Ratones , Simulación del Acoplamiento MolecularRESUMEN
The unique electron deficiency and coordination property of boron led to a wide range of applications in chemistry, energy research, materials science and the life sciences. The use of boron-containing compounds as pharmaceutical agents has a long history, and recent developments have produced encouraging strides. Boron agents have been used for both radiotherapy and chemotherapy. In radiotherapy, boron neutron capture therapy (BNCT) has been investigated to treat various types of tumors, such as glioblastoma multiforme (GBM) of brain, head and neck tumors, etc. Boron agents playing essential roles in such treatments and other well-established areas have been discussed elsewhere. Organoboron compounds used to treat various diseases besides tumor treatments through BNCT technology have also marked an important milestone. Following the clinical introduction of bortezomib as an anti-cancer agent, benzoxaborole drugs, tavaborole and crisaborole, have been approved for clinical use in the treatments of onychomycosis and atopic dermatitis. Some heterocyclic organoboron compounds represent potentially promising candidates for anti-infective drugs. This review highlights the clinical applications and perspectives of organoboron compounds with the natural boron atoms in disease treatments without neutron irradiation. The main topic focuses on the therapeutic applications of organoboron compounds in the diseases of tuberculosis and antifungal activity, malaria, neglected tropical diseases and cryptosporidiosis and toxoplasmosis.
Asunto(s)
Boro/química , Boro/metabolismo , Boro/farmacología , Antibacterianos/farmacología , Antiparasitarios/farmacología , Terapia por Captura de Neutrón de Boro/métodos , Terapia por Captura de Neutrón de Boro/tendencias , Bortezomib/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Criptosporidiosis/tratamiento farmacológico , Dermatitis Atópica/tratamiento farmacológico , Eccema/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Humanos , Malaria/tratamiento farmacológico , Onicomicosis/tratamiento farmacológico , Toxoplasmosis/tratamiento farmacológico , Tuberculosis/tratamiento farmacológicoRESUMEN
In comparison with pristine sinomenine and carborane precursors, the calculations of molecular docking with matrix metalloproteinases (MMPs) and methylcarboranyl-n-butyl sinomenine showed improved interactions. Accordingly, methylcarboranyl-n-butyl sinomenine shows a high potential in the treatment of rheumatoid arthritis (RA) in the presence of slow neutrons. The reaction of potassium salt of sinomenie, which is generated from the deprotonation of sinomenine (1) using potassium carbonate in a solvent of N,N-dimethyl formamide, with 4-methylcarboranyl-n-butyl iodide, (2) forms methylcarboranyl-n-butyl sinomenine (3) in 54.3% yield as a new product. This new compound was characterized by 1H, 13C, and 11B NMR spectroscopy, FT-IR spectroscopy, and elemental analyses to confirm its molecular composition. In addition to molecular docking interactions with MMPs, the in vitro killing effects of 3, along with its toxicity measurements, exhibited its potential to be the new drug delivery agent for boron neutron capture synovectomy (BNCS) and boron neutron capture therapy (BNCT) for the treatment of rheumatoid arthritis (RA) and cancers in the presence of slow neutrons, respectively.
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Antineoplásicos/química , Antirreumáticos/química , Antirreumáticos/farmacología , Terapia por Captura de Neutrón de Boro/métodos , Morfinanos/química , Animales , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antirreumáticos/síntesis química , Boro/farmacocinética , Línea Celular Tumoral , Evaluación Preclínica de Medicamentos , Ensayos de Selección de Medicamentos Antitumorales , Espectroscopía de Resonancia Magnética , Metaloproteinasa 1 de la Matriz/química , Metaloproteinasa 1 de la Matriz/metabolismo , Metaloproteinasa 13 de la Matriz/química , Metaloproteinasa 13 de la Matriz/metabolismo , Simulación del Acoplamiento Molecular , Ratas , Espectroscopía Infrarroja por Transformada de Fourier , Sinoviocitos/efectos de los fármacosRESUMEN
Boron compounds now have many applications in a number of fields, including Medicinal Chemistry. Although the uses of boron compounds in pharmacological science have been recognized several decades ago, surprisingly few are found in pharmaceutical drugs. The boron-containing compounds epitomize a new class for medicinal chemists to use in their drug designs. Carboranes are a class of organometallic compounds containing carbon (C), boron (B), and hydrogen (H) and are the most widely studied boron compounds in medicinal chemistry. Additionally, other boron-based compounds are of great interest, such as dodecaborate anions, metallacarboranes and metallaboranes. The boron neutron capture therapy (BNCT) has been utilized for cancer treatment from last decade, where chemotherapy and radiation have their own shortcomings. However, the improvement in the already existing (BPA and/or BSH) localized delivery agents or new tumor-targeted compounds are required before realizing the full clinical potential of BNCT. The work outlined in this short review addresses the advancements in boron containing compounds. Here, we have focused on the possible clinical implications of the new and improved boron-based biologically active compounds for BNCT that are reported to have in vivo and/or in vitro efficacy.
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Terapia por Captura de Neutrón de Boro/métodos , Boro/química , Animales , Carbono/química , Humanos , Hidrógeno/químicaRESUMEN
Reactions of closo-1-Me-2-Iodobutyl-1,2-closo-dicarborane, 1-Me-2-I(CH2)4-C2B10H10, with l-dopa methyl ester can produce carboranyl l-dopa methyl esters in 54% yield in the presence of sodium hydroxide. The appended closo-carboranes can be decapitated with sodium hydroxide in a mixed solvent of ethanol and deionized water to produce highly water-soluble carboranyl levodopa in 64% yield. All the new compounds were characterized by 1H, 13C, 11B NMR, FT-IR spectroscopy and elemental analysis. The highly water soluble carboranyl levodopa 4 shows promising efficacy of anti-tumors in vitro in the presence of slow neutron beams.
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Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Dopaminérgicos/química , Gliosarcoma/tratamiento farmacológico , Levodopa/química , Apoptosis , Proliferación Celular , Gliosarcoma/patología , Humanos , Técnicas In Vitro , Células Tumorales CultivadasRESUMEN
The practical application of boron isocyanates has been hindered by their extremely high sensitivity and reactivity toward air and moisture. A convenient synthetic method in a suitable liquid media is reported for practical utilization of boron isocyanates. According to NMR studies, the in situ generated boron isocyanates can be stored for at least one month under an inert atmosphere at -20 °C without noticeable decomposition. The boron tri(isocyanate) (B(NCO)3 ) was converted into boron nanoparticles by reduction with hydrogen under mild reaction conditions.
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Due to the topological effect, cyclic polymers demonstrate different and unique physical and biological properties in comparison with linear counterparts having the same molecular-weight range. With advanced synthetic and analytic technologies, cyclic polymers with different topologies, e.g. multicyclic polymers, have been reported and well characterized. For example, various cyclic DNA and related structures, such as cyclic duplexes, have been prepared conveniently by click chemistry. These types of DNA have increased resistance to enzymatic degradation and have high thermodynamic stability, and thus, have potential therapeutic applications. In addition, cyclic polymers have also been used to prepare organic-inorganic hybrids for applications in catalysis, e.g. catalyst supports. Due to developments in synthetic technology, highly pure cyclic polymers could now be produced in large scale. Therefore, we anticipate discovering more applications in the near future. Despite their promise, cyclic polymers are still less explored than linear polymers like polyolefins and polycarbonates, which are widely used in daily life. Some critical issues, including controlling the molecular weight and finding suitable applications, remain big challenges in the cyclic-polymer field. This review briefly summarizes the commonly used synthetic methodologies and focuses more on the attractive functional materials and their biological properties and potential applications.
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An efficient amide synthesis by atmospheric pressure aminocarbonylation using palladium nanoparticles supported on MOF-5 is reported. Interestingly, only 0.5 wt% palladium loading was required to achieve high yields. The catalyst is recyclable and offers negligible palladium leaching.
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Hidrocarburos Aromáticos/química , Yoduros/química , Nanopartículas/química , Compuestos Organometálicos/química , Paladio/química , Aminas/química , Presión Atmosférica , Catálisis , Hidrocarburos Aromáticos/síntesis química , Yoduros/síntesis química , Nanopartículas/ultraestructuraRESUMEN
Well-dispersed palladium (0) nanoparticles stabilized with phosphonium based ionic liquid were synthesized conveniently and fully characterized. A catalyst system comprising of the Pd(0) nanoparticles and a base was found to be recyclable and efficient for the aminocarbonylation reaction of aryl iodide in ionic liquid media. In the presence of potassium tert-butyloxide, for the relatively stable aryl chloride and bromide substrates, medium activities were achieved for the catalyst. The catalyst composites can be recycled at least five times with sustained activity.
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Nanopartículas/química , Paladio/química , Aminas/química , Catálisis , Hidrocarburos Aromáticos/química , Líquidos Iónicos/química , Nanopartículas/ultraestructura , Compuestos Organofosforados/químicaRESUMEN
This review covers the application of cycloaddition reactions in forming the boron-containing compounds such as symmetric star-shaped boron-enriched dendritic molecules, nano-structured boron materials and aromatic boronic esters. The resulting boron compounds are potentially important reagents for both materials science and medical applications such as in boron neutron capture therapy (BNCT) in cancer treatment and as drug delivery agents and synthetic intermediates for carbon-carbon cross-coupling reactions. In addition, the use of boron cage compounds in a number of cycloaddition reactions to synthesize unique aromatic species will be reviewed briefly.
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Compuestos de Boro/química , Compuestos de Boro/síntesis química , Boro/química , Terapia por Captura de Neutrón de Boro/métodos , Sistemas de Liberación de Medicamentos , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
In the last few decades, the synthesis and catalytic application of nanoscaled particles prepared from Group 8-10 (formerly Group VIIIB) elements have been widely explored and have achieved promising results. The innovative use of these nanoparticle catalysts may provide new opportunities in the efficient combination of conventionally used homogenous and heterogeneous catalysts. Conventional homogeneous catalysts pose extraction and recycling difficulties when dealing with metal complexes and/or ligands, whereas heterogeneous catalysts generally require more pressing experimental conditions, such as high temperatures and high pressures, to be effective. Therefore, to solve these problems, the synthesis and use of nanoparticle catalysts as replacements for conventional catalytic systems is a breakthrough owing to their improved handling and environmental and economic aspects. This Focus Review primarily addresses the catalytic applications of neutral Group 8-10 nanoparticles with an average size of less than 10 nm, and also includes a discussion of commonly used synthetic methodology.