Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.164
Filtrar
1.
Nature ; 575(7782): 336-340, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31723273

RESUMO

Organoboron reagents are important synthetic intermediates that have a key role in the construction of natural products, pharmaceuticals and organic materials1. The discovery of simpler, milder and more efficient approaches to organoborons can open additional routes to diverse substances2-5. Here we show a general method for the directed C-H borylation of arenes and heteroarenes without the use of metal catalysts. C7- and C4-borylated indoles are produced by a mild approach that is compatible with a broad range of functional groups. The mechanism, which is established by density functional theory calculations, involves BBr3 acting as both a reagent and a catalyst. The potential utility of this strategy is highlighted by the downstream transformation of the formed boron species into natural products and drug scaffolds.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Boro/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Teoria da Densidade Funcional , Descoberta de Drogas , Indóis/química , Compostos Organometálicos/química , Preparações Farmacêuticas/síntese química , Preparações Farmacêuticas/química
2.
Phys Chem Chem Phys ; 21(45): 24884-24890, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31584588

RESUMO

The controlled synthesis of hybrid two-dimensional (2D) materials and the development of atomically precise nanopore fabrication techniques have opened up entirely new possibilities for sensing applications via nanoelectronics. Here, we investigate the electronic transport properties of an in-plane hybrid graphene/h-BN device, containing a graphene nanopore, to assess its feasibility to act as a molecular sensor. The results from our calculations based on density functional theory and the non-equilibrium Green's function formalism reveal the capability to confine the electric current pathways to the two carbon wires lining either edge of the nanopore, thereby creating conditions in which the conductance is highly sensitive to any changes in the electrical potential inside the nanopore. We apply this setup to assess whether it is possible to electrically determine the base sequence in a DNA molecule. Indeed, the modulation of the device conductance reveals a characteristic fingerprint of each nucleotide, which manifests itself in a pronounced difference in the sensitivity of the four different nucleotides, thereby allowing electrical discrimination. These findings lead us to propose this device architecture as a promising nanobiosensor. While fabrication in the lab may represent a profound experimental challenge, it should nevertheless in principle be feasible with existing contemporary techniques of hybrid 2D material synthesis, in conjunction with approaches for highly controlled nanopore creation.


Assuntos
DNA/análise , Nanoporos , Nanotecnologia , Compostos de Boro/química , Teoria da Densidade Funcional , Eletricidade , Transporte de Elétrons , Grafite/química
3.
Chem Commun (Camb) ; 55(90): 13518-13521, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31608902

RESUMO

A distyryl boron dipyrromethene based photosensitiser substituted with 1,2,4,5-tetrazine and alkyne moieties was prepared. Through site-specific bioorthogonal reactions with the complementary functional tags anchored on the membrane of A431 human epidermoid carcinoma cells, this versatile photosensitiser exhibited enhanced cellular uptake and photocytotoxicity. The bioorthogonal ligation was also demonstrated in tumour-bearing nude mice.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Porfobilinogênio/análogos & derivados , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , Camundongos Nus , Estrutura Molecular , Neoplasias Experimentais/tratamento farmacológico , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Imagem Óptica , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Porfobilinogênio/síntese química , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
4.
Phys Chem Chem Phys ; 21(36): 19944-19950, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31475699

RESUMO

In this manuscript the ability of closo-carboranes to establish CHπ and BHπ interactions with several aromatic moieties exhibiting different electronic natures has been evaluated at the PBE0-D3/def2-TZVP level of theory. We have used the three closo isomers (ortho-, meta-, and para-) and benzene, trifluorobenzene and hexafluorobenzene as aromatic systems. Furthermore, we have used Bader's theory of "atoms in molecules" to further describe and characterize the noncovalent interactions described herein from a charge-density perspective. Finally, several biological examples retrieved from the PDB are also included, highlighting the impact of these interactions in the binding affinity of boron tracedrugs.


Assuntos
Compostos de Boro/química , Modelos Químicos , Cristalização , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/metabolismo , Vitamina D/química , Vitamina D/metabolismo , Raios X
5.
Chem Commun (Camb) ; 55(77): 11567-11570, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31495830

RESUMO

A small series of fluorescent lysosome-targeting probes based on the BODIPY fluorophore and containing morpholine and nitro groups were rationally designed. These probes emitted light from green to NIR wavelengths, and provided specificity for imaging the lysosomes of hypoxic cells. The electron-withdrawing nitrophenyl group at the meso position was found to lead to highly efficient nonradiative decay of the S1 state, and hence a recovery of fluorescence when reduction of the nitro group occurred under hypoxic conditions.


Assuntos
Compostos de Boro/química , Hipóxia Celular , Corantes Fluorescentes/química , Lisossomos/metabolismo , Teoria da Densidade Funcional , Células Hep G2 , Humanos , Luz , Morfolinas/química , Espectrometria de Fluorescência/métodos
6.
Chem Commun (Camb) ; 55(73): 10920-10923, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31441463

RESUMO

The development of new NIR-II fluorophores, particularly those with facile syntheses, high fluorescence quantum yields, and stable and tunable photophysical properties, is challenging. Herein, we report a new class of small molecular NIR-II fluorophores based on aza-dipyrromethene boron difluoride (aza-BODIPY) dyes. We demonstrate promising photophysical properties of these dyes, such as large Stokes shift, superior photostability, and good fluorescence brightness as nanoparticles in aqueous solution. Because of these properties and high resolution and deep penetration NIR-II imaging ability, the aza-BODIPY based dyes show great potential as NIR-II imaging agents.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Imagem Óptica/métodos , Pirróis/química , Animais , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Compostos de Boro/toxicidade , Linhagem Celular Tumoral , Teoria da Densidade Funcional , Desenho de Drogas , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Corantes Fluorescentes/toxicidade , Raios Infravermelhos , Camundongos , Modelos Químicos , Nanopartículas/química , Poloxâmero/química , Pirróis/síntese química , Pirróis/efeitos da radiação , Pirróis/toxicidade
7.
J Enzyme Inhib Med Chem ; 34(1): 1498-1505, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31423863

RESUMO

Recent studies identified the benzoxaborole moiety as a new zinc-binding group able to interact with carbonic anhydrase (CA) active site. Here, we report a structural analysis of benzoxaboroles containing urea/thiourea groups, showing that these molecules are very versatile since they can bind the enzyme assuming different binding conformations and coordination geometries of the catalytic zinc ion. In addition, theoretical calculations of binding free energy were performed highlighting the key role of specific residues for protein-inhibitor recognition. Overall, these data are very useful for the development of new inhibitors with higher selectivity and efficacy for various CAs.


Assuntos
Compostos de Boro/farmacologia , Inibidores da Anidrase Carbônica/farmacologia , Anidrases Carbônicas/metabolismo , Compostos de Boro/síntese química , Compostos de Boro/química , Inibidores da Anidrase Carbônica/síntese química , Inibidores da Anidrase Carbônica/química , Cristalografia por Raios X , Relação Dose-Resposta a Droga , Humanos , Modelos Moleculares , Conformação Molecular , Relação Estrutura-Atividade
8.
Pharm Res ; 36(10): 144, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31392417

RESUMO

PURPOSE: Boron neutron capture therapy (BNCT) has the potential to become a viable cancer treatment modality, but its clinical translation requires sufficient tumor boron delivery while minimizing nonspecific accumulation. METHODS: Thermal sensitive liposomes (TSLs) were designed to have a stable drug payload at physiological temperatures but engineered to have high permeability under mild hyperthermia. RESULTS: We found that TSLs improved the tumor-specific delivery of boronophenylalanine (BPA) and boronated 2-nitroimidazole derivative B-381 in D54 glioma cells. Uniquely, the 2-nitroimidazole moiety extended the tumor retention of boron content compared to BPA. CONCLUSION: This is the first study to show the delivery of boronated compounds using TSLs for BNCT, and these results will provide the basis of future clinical trials using TSLs for BNCT.


Assuntos
Compostos de Boro/química , Terapia por Captura de Nêutron de Boro , Lipossomos/química , Animais , Antineoplásicos/química , Compostos de Boro/administração & dosagem , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral , Neoplasias do Sistema Nervoso Central/metabolismo , Doxorrubicina/química , Liberação Controlada de Fármacos , Feminino , Glioma/metabolismo , Humanos , Hipertermia Induzida , Camundongos Nus , Nitroimidazóis/administração & dosagem , Nitroimidazóis/química , Tamanho da Partícula , Fenilalanina/administração & dosagem , Fenilalanina/análogos & derivados , Fenilalanina/química , Fosfolipídeos/química , Temperatura Ambiente , Distribuição Tecidual
9.
Photochem Photobiol Sci ; 18(10): 2381-2396, 2019 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-31432864

RESUMO

The synthesis, photophysics, and photobiological activities of a series of novel neutral heteroleptic cyclometalated iridium(iii) complexes incorporating boron dipyrromethene (BODIPY) substituted N-heterocyclic carbene (NHC) ligands (Ir1-Ir5) are reported. The effect of the substitution position of BODIPY on the NHC ligands, either on C4 of the phenyl ring (Ir1-Ir3) or C5 of the benzimidazole unit (Ir4 and Ir5), and its linker type (single or triple bond) on the photophysical properties was studied. Ir1-Ir5 exhibited BODIPY-localized intense 1IL (intraligand transition)/1MLCT (metal-to-ligand charge transfer) absorption at 530-543 nm and 1,3IL/1,3CT (charge transfer) emission at 582-610 nm. The nanosecond transient absorption results revealed that the lowest triplet excited states of these complexes were the BODIPY-localized 3π,π* states. Complexes Ir4 and Ir5 exhibited blue-shifted 1IL absorption and 1,3IL/1,3CT emission bands compared to the corresponding absorption and emission bands in complexes Ir1 and Ir3. However, replacing the methyl substituents on N3 of benzimidazole in complexes Ir1 and Ir4 with oligoether substituents in Ir3 and Ir5, respectively, did not impact the energies of the low-energy absorption and emission bands in the corresponding complexes. Water-soluble complexes Ir3 and Ir5 have been explored as photosensitizers for in vitro photodynamic therapy (PDT) effects toward human SKMEL28 melanoma cells. Ir3 showed no dark cytotoxicity (EC50 > 300 µM) but good photocytotoxic activity (9.66 ± 0.28 µM), whereas Ir5 exhibited a higher dark cytotoxicity (20.2 ± 1.26 µM) and excellent photocytotoxicity (0.15 ± 0.01 µM). The phototherapeutic indices with visible light (400-700 nm) activation were >31 for Ir3 and 135 for Ir5. Ir3 and Ir5 displayed 1O2 quantum yields of 38% and 22% in CH3CN, respectively, upon 450 nm excitation. Ir5 was more effective at generating reactive oxygen species (ROS) in vitro. Ir5 was also active against Staphylococcus aureus upon visible light activation, with a phototherapeutic index of >15 and EC50 value of 6.67 µM. These photobiological activities demonstrated that these neutral Ir(iii) complexes are promising in vitro PDT reagents, and substitution at C5 on the benzimidazole group of the NHC ligand was superior to C4 substitution on the phenyl ring.


Assuntos
Compostos de Boro/química , Complexos de Coordenação/química , Irídio/química , Metano/análogos & derivados , Fármacos Fotossensibilizantes/síntese química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Humanos , Ligantes , Luz , Metano/química , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Teoria Quântica , Espécies Reativas de Oxigênio/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Nanomedicina Teranóstica
10.
J Chem Theory Comput ; 15(9): 5046-5057, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31390517

RESUMO

Halogenated BODIPY derivatives are emerging as important candidates for photodynamic therapy of cancer cells due to their high triplet quantum yield. We probed fundamental photophysical properties and interactions with biological environments of such photosensitizers. To this end, we employed static TD-DFT quantum chemical calculations as well as TD-DFT surface hopping molecular dynamics on potential energy surfaces resulting from the eigenstates of the total electronic Hamiltonian including the spin-orbit (SO) coupling. Matrix elements of an effective one-electron spin-orbit Hamiltonian between singlet and triplet configuration interaction singles (CIS) auxiliary wave functions are calculated using a new code capable of dealing with singlets and both restricted and unrestricted triplets built up from up to three different and independent sets of (singlet, alpha, and beta) molecular orbitals. The interaction with a biological environment was addressed by using classical molecular dynamics (MD) in a scheme that implicitly accounts for electronically excited states. For the surface hopping trajectories, an accelerated MD approach was used, in which the SO couplings are scaled up, to make the calculations computationally feasible, and the lifetimes are extrapolated back to unscaled SO couplings. The lifetime of the first excited singlet state estimated by semiclassical surface hopping simulations is 139 ± 75 ps. Classical MD demonstrates that halogenated BODIPY in the ground state, in contrast to the unsubstituted one, is stable in the headgroup region of minimalistic cell membrane models, and while in the triplet state, the molecule relocates to the membrane interior ready for further steps of photodynamic therapy.


Assuntos
Compostos de Boro/química , Simulação de Dinâmica Molecular , Fotoquimioterapia , Teoria da Densidade Funcional , Processos Fotoquímicos , Fármacos Fotossensibilizantes/química , Teoria Quântica , Propriedades de Superfície
11.
Chem Commun (Camb) ; 55(58): 8494-8497, 2019 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-31268095

RESUMO

A rational strategy was reported to construct boranil complexes (DPFB derivatives) with unique aggregation-induced emission effects by installing phenyl rings in the anil ligand as the intramolecular rotors. In view of the good biocompatibility and suitable lipophilicity, DPFB derivatives can serve as excellent fluorescent probes for specific imaging of lipid droplets in living cells and yolk lipids in zebrafish.


Assuntos
Compostos de Anilina/química , Compostos de Boro/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Gotículas Lipídicas/metabolismo , Compostos de Anilina/síntese química , Animais , Compostos de Boro/síntese química , Complexos de Coordenação/síntese química , Fluorescência , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Ligantes , Microscopia Confocal/métodos , Estrutura Molecular , Peixe-Zebra
12.
Chem Commun (Camb) ; 55(59): 8564-8566, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31271158

RESUMO

Diphenylalanine (FF), as the smallest unit and core recognition motif of ß-amyloid (Aß), could self-assemble into nanofibers, which induces an early onset of Alzheimer's disease (AD). Green/near-infrared fluorescent BODIPY probes were designed and synthesized to detect FF-assembly, providing unique insights into the chemical and molecular mechanism of Aß aggregation and drug development for AD.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Fenilalanina/análogos & derivados , Técnicas Biossensoriais/métodos , Compostos de Boro/síntese química , Corantes Fluorescentes/síntese química , Nanofibras/química , Fenilalanina/análise , Fenilalanina/química , Multimerização Proteica
13.
Inorg Chem ; 58(14): 9067-9075, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31268715

RESUMO

The binuclear platinum(II) boron-dipyrromethene (BODIPY) complex [{Pt(dach)}2(µ-Dcrb)] (DP), where dach is 1,2-diaminocyclohexane and H4Dcrb is a morpholine-conjugated BODIPY-linked dicatechol bridging ligand, was prepared for lysosome organelle targeting and near-IR (NIR) light (600-720 nm) induced photocytotoxic activity. The platinum complex [Pt(dach)(cat)] (CP), where H2cat is catechol, was synthesized and used as a control complex without bearing the BODIPY unit. The complex DP displayed a band at 660 nm (ε = 2.1 × 104 M-1 cm-1) in the red region of the UV-visible spectrum recorded in 10% dimethyl sulfoxide/Dulbecco's Modified Eagle's Medium (DMSO/DMEM, pH 7.2). The complex DP and the BODIPY ligand displayed emission in 10% DMSO-DMEM (pH 7.2) giving an λem value of 668 nm (λex = 650 nm) with a ΦF value of 0.02 for DP and 0.16 for H4Dcrb (ΦF, fluorescence quantum yield). Titration experiments using 1,3-diphenylisobenzofuran (DPBF) indicated that the complex DP and H4Dcrb on irradiation with near-IR light of 600-720 nm generated singlet oxygen (1O2) as the ROS (reactive oxygen species). The complex DP showed significant lysosomal localization and remarkable apoptotic photodynamic therapy (PDT) effects, giving half-maximal inhibitory concentration values (IC50) within 0.6-3.4 µM in HeLa cervical cancer, A549 lung cancer, and MDA-MB231 multidrug resistant cancer cells, while being essentially nontoxic in the dark and in the HPL1D immortalized lung epithelial normal cells. The acridine orange assay using A549 cells showed lysosomal membrane permeabilization by the complex DP under near-IR light (600-720 nm). This complex on near-IR light (600-720 nm) activation in A549 cells induced apoptotic cell death, as observed from an Annexin-V FITC assay.


Assuntos
Compostos de Boro/química , Lisossomos/química , Fotoquimioterapia , Compostos de Platina/química , Pirróis/química , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Cristalografia por Raios X , Humanos , Potenciais da Membrana/efeitos dos fármacos , Estrutura Molecular , Compostos de Platina/farmacologia
14.
Eur J Med Chem ; 179: 791-804, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31288128

RESUMO

Advances in the field of boron chemistry have expanded the application of this element in Medicinal Chemistry. Boron-containing compounds represent a new class for medicinal chemists to use in their drug designs. Bortezomib (Velcade®), a dipeptide boronic acid approved by the FDA in 2003 for treatment of multiple myeloma, paved the way for the discovery of new boron-containing compounds. After its approval, two other boron-containing compounds have been approved, tavaborole (Kerydin®) for the treatment of onychomicosis and crisaborole (Eucrisa®) for the treatment of mild to moderate atopic dermatitis. A number of boron-containing compounds have been described and evaluated for a plethora of therapeutic applications. The present review is intended to highlight the recent advances related to boron-containing compounds and their therapeutic applications. Here, we focused only in those most biologically active compounds with proven in vitro and/or in vivo efficacy in the therapeutic area published in the last years.


Assuntos
Compostos de Boro/uso terapêutico , Bortezomib/uso terapêutico , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Dermatite Atópica/tratamento farmacológico , Mieloma Múltiplo/tratamento farmacológico , Onicomicose/tratamento farmacológico , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Bortezomib/síntese química , Bortezomib/química , Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Desenho de Drogas , Humanos
15.
Anal Bioanal Chem ; 411(23): 6165-6172, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31312882

RESUMO

The copper(II) ion (Cu2+) has played an indispensable role in diverse kinds of functional physiological processes of organisms, which has become of growing interest. Despite the fact that numerous Cu2+ test papers using fluorescent probes have been fabricated, sensors featuring the ratiometric property that integrates quenched probes and an inner standard dye are rarely reported. Herein, a two-component ratiometric sensor in a paper-based device is proposed to realize highly selective Cu2+ detection. To overcome shortcomings such as low signal-to-noise ratio and incorrect response of the quenching probe, a novel BODIPY-based turn-off probe (P2017) is designed and introduced into the paper-based device with better water solubility and selectivity for Cu2+ detection. Furthermore, a reference dye (B001), exhibiting an emission at 690 nm when the excitation wavelength is 480 nm, is also introduced into the paper-based device. These two components can enhance the quality of the signal as P2017 is sensitively quenched by Cu2+, while B001 with a photostable property, serving as an internal benchmark, is unable to react with Cu2+. The results indicated that the two components provided a new concept for optimizing paper-based device fabrication and developing accurate, simple, and inexpensive Cu2+ detection methods, which could be potentially applied to monitor human health and the environment in remote areas. Graphical abstract.


Assuntos
Técnicas Biossensoriais/instrumentação , Compostos de Boro/química , Cobre/análise , Corantes Fluorescentes/química , Papel , Cátions Bivalentes/análise , Desenho de Equipamento , Células Hep G2 , Humanos
16.
Phys Rev Lett ; 122(25): 257402, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31347870

RESUMO

We uncover a novel phenomenon from a recent artificial light-harvesting experiment [P.-Z. Chen et al., Angew. Chem., Int. Ed. Engl. 55, 2759 (2016)ACIEAY0570-083310.1002/anie.201510503] on organic nanocrystals of self-assembled difluoroboron chromophores. A resonant confinement of a polariton under strong photon-exciton coupling is predicted to exist within the microcavity of the crystal's own natural boundaries. Moreover, the radiative energy of a localized exciton falls into the spectrum of confinement. Hence, in the experiment, the spontaneous emission of an excited pigment would undergo a two-step process. It should first decay to an excitonic polariton trapped by the cavity resonance. The intermediate polariton could then funnel the energy directly to a doped acceptor, leading to the over 90% transfer efficiency observed at less than 1/1000 acceptor/donor ratio. The proposed mechanism is supported by parameter-free analyses entirely based on experiment data. Our finding may imply possible polariton-mediated pathways for energy transfers in biological photosynthesis.


Assuntos
Modelos Químicos , Nanopartículas/química , Fotossíntese , Materiais Biomiméticos/química , Compostos de Boro/química , Transferência de Energia , Complexos de Proteínas Captadores de Luz/química
17.
Photochem Photobiol Sci ; 18(8): 2003-2011, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31268087

RESUMO

Here we report the activatable photosensitizer BromoAcroB, a brominated BODIPY dye incorporating a reactive acrolein warhead. The acrolein moiety serves as an intramolecular switch, deactivating the BODIPY dye in its singlet and triplet excited states via internal conversion. Thiolate addition to this moiety disables the intramolecular quenching mechanism restoring the photosensitizing properties of the parent dye, characterized by a quantum yield of singlet oxygen photosensitization of 0.69 ± 0.02. In cell cultures, and upon thiol adduct formation, BromoAcroB induced light-dependent cell death in MRC-5 and HeLa cell lines. Using fluorescence microscopy and upon measuring the low yet non-negligible emission of the activated compound, we show that the phototoxicity of the dormant photosensitizer correlated with the quantity of BromoAcroB adducts generated. BromoAcroB thus serves as a dormant photosensitizer sensitive to intracellular electrophile response. Our results highlight the effective control of a triplet state process by modulation of an unsaturated moiety on the BODIPY scaffold and underscore the mechanistic opportunities arising for controlled singlet oxygen production in cells specifically sensitive to electrophile stress.


Assuntos
Acroleína/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Cisteína/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/farmacologia , Acroleína/química , Compostos de Boro/química , Morte Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cisteína/química , Células HeLa , Humanos , Luz , Microscopia de Fluorescência , Estrutura Molecular , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Teoria Quântica , Oxigênio Singlete/química
18.
Photochem Photobiol Sci ; 18(8): 2012-2022, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31282525

RESUMO

Organic-metal complexes are promising molecules for use in photodynamic therapy (PDT). The aim of this study was to investigate in vitro effects of novel Ru(ii) and Ir(iii) BODIPY complexes for PDT. These hybrid organic-metal molecules (Ru-BD and Ir-BD) have been synthesized via reactions of a BODIPY precursor (BD) with a phenanthroline unit bearing Ru(ii) (3) and novel Ir(iii) (4) compounds. The crystal structures of the new distyryl BODIPY (BD) and Ru(ii) complex (3) are also reported. The photophysical and singlet oxygen generation properties of Ru-BD and Ir-BD were investigated in comparison with unsubstituted BODIPY (BD). Moreover, Ru-BD and Ir-BD have been biologically evaluated in vitro in chronic myeloid leukemia and cervical cancer cell lines in terms of photodynamic therapy efficacy in the presence of BD control. These complexes were not toxic in the dark but red light was needed to induce cell death. These data support the fact that Ru-BD could be accepted as a valuable photosensitizer-drug for further PDT treatment.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Corantes/farmacologia , Compostos Organometálicos/farmacologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Corantes/síntese química , Corantes/química , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Irídio/farmacologia , Modelos Moleculares , Estrutura Molecular , Compostos Organometálicos/síntese química , Compostos Organometálicos/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Rutênio/química , Rutênio/farmacologia , Oxigênio Singlete/análise , Oxigênio Singlete/metabolismo , Células Tumorais Cultivadas
19.
Molecules ; 24(11)2019 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-31146429

RESUMO

A concise synthetic route from methylmalonate to a tetravalent aliphatic scaffold has been developed. The ensuing tetra-tethered derivative is equipped with two hydroxyl groups, as well as orthogonal alkene and alkyne functionalities. The usefulness of the scaffold has been demonstrated with the preparation of two representative multivalent derivatives: (i) a tetravalent compound containing two D-mannose units, one fluorescent boron-dipyrromethene (BODIPY) dye and a suitably functionalized amino acid and (ii) by way of dimerization and saponification, a water-soluble tetramannan derivative containing two fluorescent BODIPY units. Additionally, photophysical measurements conducted on these derivatives support the viability of the herein designed single and double BODIPY-labeled carbohydrate-based clusters as fluorescent markers.


Assuntos
Compostos de Boro/química , Carboidratos/química , Malonatos/química , Técnicas de Química Sintética , Estrutura Molecular , Análise Espectral
20.
Int J Nanomedicine ; 14: 3543-3555, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190811

RESUMO

Background: In recent years, non-invasive imaging technologies for early cancer detection have drawn worldwide attention. In this study, an antinucleolin aptamer, AS1411, was successfully conjugated to BODIPY-labeled chitosan and studied on T47D and HEK-293 cell lines. Methods: After conjugation of the aptamer to chitosan nanoparticles and purification, its structure was confirmed using atomic force microscopy (AFM), electrophoretic light scattering (ELS) and dynamic light scattering (DLS). Results of AFM, DLS and ELS of both conjugation and chitosan were compared for confirmation of conjugation. Conjugates were mixed with BODIPY FL fluorescent dye, purified and lyophilized. The labeled conjugate was characterized using Fourier-transform infrared spectroscopy, ultraviolet-visible spectroscopy, ELS and DLS. In vitro cellular uptake and cytotoxic effects of BODIPY-labeled chitosan-AS1411 aptamer conjugates were evaluated using the XTT assay on T47D and HEK-293 cells and flow cytometry on T47D cells. Results: The data showed that uptake of BODIPY-labeled chitosan-AS1411 aptamer conjugate was satisfactory. Moreover, there was no statistically significant cytotoxicity of the conjugate on either cell line. Conclusion: The outcomes confirmed the potential application of this new targeted imaging agent as a novel cancer diagnostic agent for molecular imaging.


Assuntos
Compostos de Boro/química , Quitosana/química , Imagem Molecular/métodos , Nanopartículas/química , Oligodesoxirribonucleotídeos/química , Tamanho da Partícula , Aptâmeros de Nucleotídeos/química , Linhagem Celular Tumoral , Proliferação de Células , Endocitose , Fluorescência , Corantes Fluorescentes/química , Células HEK293 , Humanos , Microscopia de Força Atômica , Nanoconjugados/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA