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1.
Org Biomol Chem ; 18(4): 707-714, 2020 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-31907494

RESUMO

Fluorescence bioimaging is very significant in studying biological processes. Fluorescent nanoparticles (NPs) manufactured from aggregation-induced emission (AIE) materials, as promising candidates, have attracted more attention. However, it is still a challenge to explore suitable AIE NPs for bioimaging. Herein, we synthesized pyrazoline-BODIPY (PZL-BDP) with a donor and acceptor (D-A) structure by a condensation reaction, cultured its single crystal, and studied its twisted intramolecular charge transfer (TICT) and AIE effects. PZL-BDP could self-assemble to form red fluorescent nanoparticles (PZL-BDP NPs) which showed a good fluorescence quantum yield of 15.8% in water. PZL-BDP NPs with excellent stability and biocompatibility exhibited a large Stokes shift (Δλ = 111 nm) which resulted in the reduction of external interference and enhancement of the fluorescence contrast. Furthermore, these nanoparticles could be readily internalized by HeLa cells and they stain the cells in just five seconds, indicating an ultrafast bioimaging protocol. Moreover, long-term tracking fluorescence signals in vivo for about 12 days were obtained. The bright red fluorescence, ultrafast cell staining ability, and long-term in vivo tracking competence outline the great potential of rational design nanomaterials with AIE characteristics for monitoring biological processes.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Nanopartículas/química , Pirazóis/química , Animais , Compostos de Boro/síntese química , Compostos de Boro/toxicidade , Linhagem Celular Tumoral , Cor , Feminino , Fluorescência , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/toxicidade , Humanos , Camundongos , Nanopartículas/toxicidade , Neoplasias/diagnóstico por imagem , Imagem Óptica/métodos , Pirazóis/síntese química , Pirazóis/toxicidade
2.
J Med Chem ; 63(4): 1699-1708, 2020 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-31967820

RESUMO

Singlet oxygen can severely damage biological tissue, which is exploited in photodynamic therapy (PDT). In PDT, the effective range is limited by the distribution of the photosensitizer (PS) and the illuminated area. However, no distinction is made between healthy and pathological tissue, which can cause undesired damage. This encouraged us to exploit the more acidic pH of cancerous tissue and design pH-controllable singlet oxygen-generating boron-dipyrromethene (BODIPY) dyes. A pH sensitivity of the dyes is achieved by the introduction of an electronically decoupled, photoinduced electron transfer (PET)-capable subunit in meso-position of the BODIPY core. To favor triplet-state formation as required for singlet oxygen generation, iodine substituents were introduced at the chromophore core. The resulting pH-controlled singlet oxygen-generating dyes with pKa values in the physiological range were subsequently assessed regarding their potential as pH-controlled PS for PDT. Using HeLa cells, we could successfully demonstrate markedly different pH-dependent cytotoxicities upon illumination.


Assuntos
Compostos de Boro/farmacologia , Corantes Fluorescentes/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Oxigênio Singlete/metabolismo , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Luz , Imagem Óptica , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Nanomedicina Teranóstica
3.
Nanotechnology ; 31(21): 215101, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31978926

RESUMO

The molecular stress caused by a drug administered to treat a disorder on healthy cells appears as a side effect. In this study, we aim to understand the potential of hexagonal boron nitrides (hBNs) as a therapeutic agent to relieve the cellular stress exerted by drugs. First, the cytotoxicity of hBNs and their possible degradation product, boric acid (BA), on the embryonic mouse hippocampal cell line mHippo E-14 was assessed in a wide concentration range (4.4-440 µg ml-1) of boron including hBNs and BA for 24 and 72 h exposure. Then, cell cycle, reactive oxygen species generation, cell death mechanism and apoptotic body formation in nuclei with hBN and BA exposure were evaluated at increased concentrations and incubation times. Finally, the cells, exposed to doxorubicin (DOX), an anti-cancer chemotherapy drug, to exert oxidative stress, were treated with hBNs and BA. The results indicate that hBNs decrease the oxidative stress at the concentrations that are nontoxic to cells. The study suggests that hBNs can open new venues for their investigation to reduce or eliminate the adverse effects of toxic drugs used in the treatment of several fatal diseases including neurological disorders and cancer with their slow degradation feature.


Assuntos
Compostos de Boro/farmacologia , Doxorrubicina/efeitos adversos , Hipocampo/embriologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Compostos de Boro/síntese química , Compostos de Boro/química , Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Nanoestruturas , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
4.
Chemistry ; 26(19): 4261-4268, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31793681

RESUMO

A series of carbazole-based boron dipyrromethenes (BODIPYs) 2 a-g bearing binaphthyl units have been synthesized by the Et2 AlCl-mediated reaction of the corresponding BODIPY difluorides 1 a-g with 1,1'-binaphthalene-2,2'-diol. Substituents such as halogen, nitrile, and amino groups were tolerated under the reaction conditions, and the reaction of the phenylethynyl-substituted 1 h gave (R,R)-3 h bearing two binaphthyl units. The chiroptical properties of these dyes with different substituents were investigated by UV/Vis, CD, fluorescence, and circularly polarized luminescence (CPL) spectroscopy. The CD spectra showed Cotton effects in the absorption region of the BODIPY moieties. In addition, they showed CPL both in solution and in the solid state. Interestingly, several dyes recorded higher glum values in the solid state, probably due to intermolecular interactions. Because (R,R)-3 h recorded relatively low glum values, the diastereomer (R,S)-3 h was prepared. The (R,S) diastereomer showed intense CPL, which suggests a synergetic effect of the two binaphthyl groups. Finally, chiral carbazole-based BODIPY dimers have been synthesized for the first time and their chiroptical properties were investigated. They showed redshifted fluorescence and CPL, which reached the near-IR (NIR) region in the solid state.


Assuntos
Compostos de Boro/síntese química , Carbazóis/síntese química , Corantes/química , Boro/química , Compostos de Boro/química , Carbazóis/química , Fluorescência , Luminescência , Estrutura Molecular , Análise Espectral
5.
Chem Commun (Camb) ; 56(7): 1078-1081, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31872834

RESUMO

A boron dipyrromethene based photosensitiser substituted with a 1,2,4,5-tetrazine moiety has been prepared of which the photoactivity can be activated upon an inverse-electron-demand Diels-Alder reaction with trans-cyclooctene derivatives. By using a biotin-conjugated trans-cyclooctene to tag the biotin-receptor-positive HeLa cells, this photosensitiser exhibits site-specific activation through cycloaddition, leading to high photocytotoxicity.


Assuntos
Compostos de Boro/farmacologia , Compostos Heterocíclicos com 1 Anel/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/efeitos da radiação , Biotina/análogos & derivados , Biotina/síntese química , Biotina/farmacologia , Compostos de Boro/síntese química , Compostos de Boro/efeitos da radiação , Linhagem Celular Tumoral , Reação de Cicloadição , Ciclo-Octanos/síntese química , Ciclo-Octanos/química , Ciclo-Octanos/farmacologia , Compostos Heterocíclicos com 1 Anel/síntese química , Compostos Heterocíclicos com 1 Anel/efeitos da radiação , Humanos , Luz , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/efeitos da radiação , Oxigênio Singlete/metabolismo
6.
Eur J Med Chem ; 185: 111858, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31718946

RESUMO

Several triterpenoid acids (betulinic, oleanolic, ursolic, glycyrrhetinic) and triterpene betulin were used as starting material to synthesize BODIPY FL adducts, and these compounds were screened for their cytotoxic activity employing several human tumor cell lines. The cytotoxicity of the compounds strongly depended on the chosen spacer between the triterpenoid core and the BODIPY FL unit. Thus, 3-O-acetyl-betulinic acid derived BODIPY FL conjugate holding an ethylendiamine spacer was cytotoxic for human breast adenocarcinoma cells MCF7 but not cytotoxic for all other cell lines.


Assuntos
Antineoplásicos/farmacologia , Compostos de Boro/farmacologia , Desenho de Fármacos , Corantes Fluorescentes/farmacologia , Triterpenos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Compostos de Boro/síntese química , Compostos de Boro/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/química , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade , Triterpenos/química
7.
Org Biomol Chem ; 18(3): 431-440, 2020 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-31850445

RESUMO

Amines are ubiquitous in the chemical industry and are present in a wide range of biological processes, motivating the development of amine-sensitive sensors. There are many turn-on amine sensors, however there are no examples of turn-on sensors that utilize the amine's ability to react by single electron transfer (SET). We investigated a new turn-on amine probe with a 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) fluorophore. BODIPY fluorescence is first preprogrammed into an off state by internal photoinduced electron transfer (PET) to an electron-deficient quinolinium ring, resulting in fluorescence quenching. At low concentrations of aliphatic amine (0 to 10 mM), this PET pathway is shut down by external SET from the amine to the photoexcited charge-transfer state of the probe and the fluorescence is turned on. At high concentrations of amine (50 mM to 1 M), we observed collisional quenching of the BODIPY fluorescence. The probe is selective for aliphatic amines over aromatic amines, and aliphatic thiols or alcohols. The three molecular processes modulate the BODIPY fluorescence in a multi-mechanistic way with two of them producing a direct response to amine concentrations. The totality of the three molecular processes produced the first example of a multi-state and dose-responsive amine sensor.


Assuntos
Aminas/análise , Compostos de Boro/química , Corantes Fluorescentes/química , Compostos de Quinolínio/química , Compostos de Boro/síntese química , Teoria da Densidade Funcional , Fluorescência , Corantes Fluorescentes/síntese química , Modelos Químicos , Compostos de Quinolínio/síntese química , Espectrometria de Fluorescência/métodos
8.
J Inorg Biochem ; 202: 110817, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31706182

RESUMO

Cis-dichloro-oxovanadium(IV) complexes [VO(L1/L2)Cl2], where L1 is N-(4-(5,5-difluoro-1,3,7,9-tetramethyl-5H-4ʎ4,5ʎ4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 1 and L2 is N-(4-(5,5-difluoro-2,8-diiodo-1,3,7,9-tetramethyl-5H-4ʎ4,5ʎ4-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-10-yl)benzyl)-1-(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine in 2) having 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene as boron-dipyrromethene (BODIPY) appended dipicolylamine bases were prepared, characterized and their photocytotoxicity studied. X-ray crystal structure of 1 showed distorted octahedral geometry with a VIVON3Cl2 core having Cl-V-Cl angle of 91.93(4)°. The complexes showed variable solution conductivity properties. They were non-electrolytes in dry DMF at 25 °C but showed 1:1 electrolytic behavior in an aqueous medium due to dissociation of one chloride ligand as evidenced from the mass spectral study. Complexes 1 and 2 showed absorption bands at 500 and 535 nm, respectively. The calf thymus DNA melting study revealed their interaction through DNA crosslinking on exposure to light which was further confirmed from the alkaline agarose gel electrophoresis using plasmid supercoiled pUC19 DNA. Complex 2 showed disruption of the mitochondrial membrane potential in the JC-1 (1,1',3,3'-tetraethyl-5,5',6,6'-tetrachloroimidacarbocyanine iodide) assay. The complexes were photocytotoxic in visible light (400-700 nm, power: 10 J cm-2) in cervical cancer HeLa and breast cancer MCF-7 cells. Complex 2 having a photoactive diiodo­boron-dipyrromethene moiety gave a singlet oxygen quantum yield (ΦΔ) value of ~0.6. It showed singlet oxygen mediated apoptotic photodynamic therapy activity with remarkably low IC50 (half maximal inhibitory concentration) value of ~0.15 µM. The cis-disposition of chlorides gave a cis-divacant 4-coordinate intermediate structure from the density functional theory (DFT) study thus mimicking the DNA crosslinking property of cisplatin.


Assuntos
Compostos de Boro , Citotoxinas , DNA , Fármacos Fotossensibilizantes , Porfobilinogênio/análogos & derivados , Vanadatos , Boro/química , Boro/farmacologia , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Cristalografia por Raios X , Citotoxinas/síntese química , Citotoxinas/química , Citotoxinas/farmacologia , DNA/química , DNA/metabolismo , Células HeLa , Humanos , Células MCF-7 , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfobilinogênio/síntese química , Porfobilinogênio/química , Porfobilinogênio/farmacologia , Vanadatos/química , Vanadatos/farmacologia
9.
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
10.
J Fluoresc ; 29(6): 1321-1329, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31713767

RESUMO

A fluorescent chemosensor including dual Bodipy units (d-BODIPY) was improved for selective copper (II) sensing in half-aqueous samples. The sensor d-BODIPY has a highly selective and sensitive detection towards Cu (II) over the studied competing for metal cations. The interaction among solutions of Cu (II) and d-BODIPY caused a crucial quenching effect in fluorescence maxima at 548 nm (λex = 470 nm) owing to the electronic trap occurring between the amide and triazole units. The quenching effect without any change in wavelength can be explained by a photoinduced electron transfer (PET) process. The binding constant (Ka) of d-BODIPY with Cu (II) was calculated and also the limit of detection of d-BODIPY for Cu (II) was 1.2 × 10-8 M. In addition, the bio-imaging in the yeast cells suggested that d-BODIPY had an excellent potential to be used to investigate Cu (II).


Assuntos
Técnicas Biossensoriais , Compostos de Boro/química , Cobre/análise , Corantes Fluorescentes/química , Imagem Óptica , Saccharomyces cerevisiae/citologia , Triazóis/química , Compostos de Boro/síntese química , Células Cultivadas , Corantes Fluorescentes/síntese química , Espectrometria de Fluorescência
11.
ACS Appl Mater Interfaces ; 11(47): 43928-43935, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31682101

RESUMO

It is a challenge to develop multifunctional theranostic agents in one molecule, which simultaneously possesses tumor imaging ability with a high signal-to-noise ratio and excellent therapeutic activity. In this work, we synthesized and screened a series of BODIPY (BDP) with various absorption and fluorescence. The interplay of the molecular structure, pH-sensitive absorption and emission, and photodynamic and photothermal activities was well studied in detail. Photoinduced electron transfer, intramolecular charge transfer, and heavy atom effect were leveraged to engineer BDP with tumor imaging and therapeutic functions. The BDP nanoparticle formulations possessed multifunctional biological features, including selective treatment of cancer cells, near-infrared fluorescence, photoacoustic and computed tomography imaging, and photodynamic and photothermal therapy, as validated by cellular and animal experiments. These results not only give a new horizon to multifunctional BDP for biological applications but also show a new way to design the organic dye for tumor imaging and phototherapy.


Assuntos
Compostos de Boro/química , Corantes Fluorescentes/química , Neoplasias/diagnóstico por imagem , Neoplasias/terapia , Fototerapia , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Compostos de Boro/síntese química , Corantes Fluorescentes/síntese química , Humanos , Concentração de Íons de Hidrogênio , Camundongos , Imagem Multimodal/instrumentação , Nanopartículas/química , Nanomedicina Teranóstica/instrumentação
12.
J Labelled Comp Radiopharm ; 62(13): 885-891, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31677180

RESUMO

Labeling agents with radioisotopes or fluorescent dyes are useful for investigating the biodistributions of biologically active proteins and peptides. Compared with molecular imaging with a single modality, dual imaging probes provide complementary information for each modality. The development of a dual radioisotope/fluorescence agent for protein labeling would thus be valuable for both preclinical and clinical applications. In this study, we designed and synthesized a radioiodinated BODIPY derivative (BODIPY-ML) with a maleimide group as a thiol-labeling agent. In the presence of N-chlorosuccinimide and 1% acetic acid, [125 I]BODIPY-ML was successfully obtained at a radiochemical yield of 42%. In conjugation studies, model proteins including RGD peptides and anti-HER2 VHH were successfully labeled with BODIPY-ML via covalent bonds. The results demonstrated the feasibility of the radioiodinated BODIPY as a dual-labeling agent via thiol groups.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Halogenação , Radioisótopos do Iodo/química , Compostos de Sulfidrila/química , Técnicas de Química Sintética , Marcação por Isótopo , Oligopeptídeos/química , Radioquímica
13.
Carbohydr Res ; 486: 107840, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689579

RESUMO

Herein, an efficient synthesis of BODIPY-α-Galactosylceramide 3, which can be used to study the cellular uptake of the potent immunostimulatory parent compound α-Galactosylceramide, is reported. Key in our synthetic strategy is the six-step synthesis of the core BODIPY scaffold (64% yield overall) and its quantitative conversion to an N-hydroxysuccinimidyl ester to facilitate conjugation and purification of the target glycolipid. For the preparation of the core of the glycolipid, the solubility of the lipid acceptor proved to be critical. The ability of BODIPY-αGalCer 3 to activate invariant natural killer cells was then demonstrated in vitro.


Assuntos
Compostos de Boro/química , Compostos de Boro/síntese química , Galactosilceramidas/química , Galactosilceramidas/metabolismo , Sondas Moleculares/química , Sondas Moleculares/síntese química , Transporte Biológico , Linhagem Celular , Técnicas de Química Sintética
14.
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
15.
Mater Sci Eng C Mater Biol Appl ; 105: 110038, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31546359

RESUMO

Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.


Assuntos
Ácido Fólico/química , Nanopartículas/química , Neoplasias Ovarianas/tratamento farmacológico , Paclitaxel/uso terapêutico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Compostos de Boro/síntese química , Compostos de Boro/química , Varredura Diferencial de Calorimetria , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Feminino , Humanos , Neoplasias Ovarianas/patologia , Paclitaxel/farmacologia , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/síntese química , Espectroscopia de Infravermelho com Transformada de Fourier
16.
Eur J Med Chem ; 183: 111685, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31525661

RESUMO

In this study, BODIPY compounds (2, 3, 5 and 6) bearing 3,4-bis(3-pyridin-3-ylpropoxy)benzyl, 4-(3-pyridin-3-ylpropoxy)benzyl groups were synthesized for the first time and further functionalized in a Knoevenagel condensation reaction with 3,4-bis(3-pyridin-3-ylpropoxy)benzaldehyde and 4-(3-pyridin-3-ylpropoxy)benzaldehyde. The water soluble derivatives of BODIPY compounds (3a and 6a) were synthesized by treating BODIPY compounds 3 and 6 with excess iodomethane in DMF. The photochemical properties and DNA binding modes of 3a and 6a were determined using ct-DNA by UV-Vis spectrophotometer and viscometer. DNA cleavage and topoisomerases inhibition properties were studied DNA using agarose gel electrophoresis. Their topoisomerase inhibition mechanisms were investigated at molecular level and correlations with the in vitro results were searched for using molecular docking method. In addition, cytotoxicity and phototoxicity of both compounds were performed on colorectal cancer cells (HCT-116) using MTT assay for 24 h. Annexin V-FITC/PI test was performed to determine the cell death mechanism of 6a induced by irradiation. Finally, 6a-loaded liposomes (LP6a) and PLGA nanoparticles (NP6a) were prepared and their cytotoxic and phototoxic effects were evaluated by MTT assay. The results claimed that 6a had great potential as photosensitizer agent for colorectal cancer owing to its photochemical, DNA interaction and phototoxic properties.


Assuntos
Antineoplásicos , Compostos de Boro , Neoplasias Colorretais/tratamento farmacológico , Fármacos Fotossensibilizantes , Inibidores da Topoisomerase , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Linhagem Celular Tumoral , Clivagem do DNA/efeitos dos fármacos , DNA Topoisomerases/metabolismo , Humanos , Simulação de Acoplamento Molecular , Fotoquimioterapia , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Inibidores da Topoisomerase/síntese química , Inibidores da Topoisomerase/química , Inibidores da Topoisomerase/farmacologia , Água
17.
Molecules ; 24(18)2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31509949

RESUMO

The amount of boron accumulated in tumor tissue plays an important role regarding the success of the boron neutron capture therapy (BNCT). In this article, we report a modular system, combining readily available starting materials, like glycine, 1,3,5-triazine and the well-known 9-mercapto-1,7-dicarba-closo-dodecaborane(12), as well as α-d-galactopyranose for increased hydrophilicity, with a novel boron-rich tris-meta-carboranyl thiol.


Assuntos
Terapia por Captura de Nêutron de Boro , Boro/farmacologia , Sistemas de Liberação de Medicamentos , Neoplasias/tratamento farmacológico , Boro/química , Compostos de Boro/síntese química , Compostos de Boro/química , Compostos de Boro/farmacologia , Ácidos Carboxílicos/química , Ácidos Carboxílicos/farmacologia , Ésteres/química , Glicina/química , Humanos , Interações Hidrofóbicas e Hidrofílicas/efeitos dos fármacos , Estrutura Molecular , Neoplasias/patologia , Compostos de Sulfidrila/química , Compostos de Sulfidrila/farmacologia , Triazinas/química , Triazinas/farmacologia
18.
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
19.
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 Fármacos , 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
20.
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 Fármacos , Humanos
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