Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Biomater Sci ; 9(18): 6183-6202, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34346411

RESUMO

Among women, ovarian cancer is the fifth most frequent type of cancer, and despite benefiting from current standard treatment plans, 90% of patients relapse in the subsequent 18 months and, eventually, perish. As a result, via embracing nanotechnological advancements in the field of medical science, researchers working in the areas of cancer therapy and imaging are looking for the next breakthrough treatment strategy to ensure lower cancer recurrence rates and improved outcomes for patients. Herein, we design a novel phototheranostic agent with optical features in the biological window of the electromagnetic spectrum via encapsulating a newly synthesized phthalocyanine dye within biocompatible protein nanoparticles, allowing the targeted fluorescence imaging and synergistic dual therapy of ovarian cancer. The nanosized agent displays great biocompatibility and enhanced aqueous biostability and photothermal activity, as well as high reactive-oxygen-species generation efficiency. To achieve the active targeting of the desired malignant tissue and suppress the rapid clearance of the photosensitive agent from the peritoneal cavity, the nanoparticles are biofunctionalized with an anti-folate receptor antibody. A2780 ovarian cancer cells are employed to confirm the improved targeting capabilities and the in vitro cytotoxic efficiency of the theranostic nanoparticles after exposure to a 660 nm LED lamp; upon measurement via MTT and flow cytometry assays, a significant 95% decrease in the total number of viable cells is seen. Additionally, the therapeutic performance of our newly designed nanoparticles was evaluated in vivo, via real-time thermal monitoring and histopathological assays, upon the irradiation of tumour-bearing mice with a 660 nm LED lamp (0.05 W cm-2). Foremost, separately from steady-state fluorescence imaging, we found that, via utilizing FLIM investigations, the differences in fluorescence lifetimes of antibody biofunctionalized and non-functionalized nanoparticles can be correlated to different intracellular localization and internalization pathways of the fluorescent agent, which is relevant for the development of a cutting-edge method for the detection of cancer cells that overexpress folate receptors at their surfaces.


Assuntos
Nanopartículas , Neoplasias Ovarianas , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Camundongos , Imagem Óptica , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/tratamento farmacológico , Fototerapia , Medicina de Precisão , Nanomedicina Teranóstica
2.
Molecules ; 26(15)2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34361832

RESUMO

In recent times, researchers have aimed for new strategies to combat cancer by the implementation of nanotechnologies in biomedical applications. This work focuses on developing protein-based nanoparticles loaded with a newly synthesized NIR emitting and absorbing phthalocyanine dye, with photodynamic and photothermal properties. More precisely, we synthesized highly reproducible bovine serum albumin-based nanoparticles (75% particle yield) through a two-step protocol and successfully encapsulated the NIR active photosensitizer agent, achieving a good loading efficiency of 91%. Making use of molecular docking simulations, we confirm that the NIR photosensitizer is well protected within the nanoparticles, docked in site I of the albumin molecule. Encouraging results were obtained for our nanoparticles towards biomedical use, thanks to their negatively charged surface (-13.6 ± 0.5 mV) and hydrodynamic diameter (25.06 ± 0.62 nm), favorable for benefitting from the enhanced permeability and retention effect; moreover, the MTT viability assay upholds the good biocompatibility of our NIR active nanoparticles. Finally, upon irradiation with an NIR 785 nm laser, the dual phototherapeutic effect of our NIR fluorescent nanoparticles was highlighted by their excellent light-to-heat conversion performance (photothermal conversion efficiency 20%) and good photothermal and size stability, supporting their further implementation as fluorescent therapeutic agents in biomedical applications.


Assuntos
Indóis/administração & dosagem , Nanopartículas/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/administração & dosagem , Soroalbumina Bovina/química , Proliferação de Células , Feminino , Humanos , Indóis/química , Luz , Simulação de Acoplamento Molecular , Nanopartículas/química , Neoplasias Ovarianas/patologia , Fármacos Fotossensibilizantes/química , Espectroscopia de Luz Próxima ao Infravermelho , Células Tumorais Cultivadas
3.
Phytochemistry ; 189: 112849, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34182200

RESUMO

Anthocyanins (AN), natural compounds daily consumed by humans, have outstanding therapeutical potential if administered topically in melanoma pathology. However, the search for efficient therapy development is still in progress, owing to the lack of complete understanding of the AN intracellular path, once they are uptaken by the cells. This target is constrained by the need for an imaging strategy that would enable their intracellular detection and localization in-situ. In this light, diphenylboric acid 2-aminoethyl (DPBA), a non-fluorescent reagent, was here successfully used to form fluorescent complexes with AN. The AN used are the cyanidin aglycon as a free standard molecule (CY), and the glycosylated compounds, extracted and purified from chokeberry fruits (AE). In solution, it was observed that the fluorescence emission increased by 39% (CY@DPBA), and by 34% (AE@DPBA), which concludes that AN form fluorescent complexes with DPBA (CY@DPBA and AE@DPBA). In addition, using NMR (nuclear magnetic resonance) spectroscopy, and HRMS (high-resolution mass spectrometry) analysis, the structure of the CY@DPBA complex was efficiently elucidated. In-vitro experiments showed that the complexes formed after the treatment proved to be non-toxic on B16-F10 cells. The sub-cellular visualization of all AN was monitored by fluorescence microscopy and flow cytometry, demonstrating detectable signals of the non-metabolized CY and glycosylated CY inside melanoma cells. This study reports that the use of DPBA to image AN intracellularly is a sensitive, non-invasive and successful method that can extend its application in broad fields like drug development or metabolism-associated mechanisms.


Assuntos
Antocianinas , Melanoma Experimental , Animais , Antocianinas/farmacologia , Linhagem Celular Tumoral , Melanoma Experimental/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , Imagem Óptica
4.
Int J Mol Sci ; 22(6)2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804193

RESUMO

We report here the synthesis and structural characterization of novel cationic (phenothiazinyl)vinyl-pyridinium (PVP) dyes, together with optical (absorption/emission) properties and their potential applicability as fluorescent labels. Convective heating, ultrasound irradiation and mechanochemical synthesis were considered as alternative synthetic methodologies proficient for overcoming drawbacks such as long reaction time, nonsatisfactory yields or solvent requirements in the synthesis of novel dye (E)-1-(3-chloropropyl)-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium bromide 3d and its N-alkyl-2-methylpyridinium precursor 1c. The trans geometry of the newly synthesized (E)-4-(2-(7-bromo-10-ethyl-10H-phenothiazin-3-yl)vinyl)-1-methylpyridin-1-ium iodide 3b and (E)-1-methyl-4-(2-(10-methyl-10H-phenothiazin-3-yl)vinyl)pyridin-1-ium tetrafluoroborate 3a' was confirmed by single crystal X-ray diffraction. A negative solvatochromism of the dyes in polar solvents was highlighted by UV-Vis spectroscopy and explanatory insights were supported by molecular modeling which suggested a better stabilization of the lowest unoccupied molecular orbitals (LUMO). The photostability of the dye 3b was investigated by irradiation at 365 nm in different solvents, while the steady-state and time-resolved fluorescence properties of dye 3b and 3a' in solid state were evaluated under one-photon excitation at 485 nm. The in vitro cytotoxicity of the new PVP dyes on B16-F10 melanoma cells was evaluated by WST-1 assay, while their intracellular localization was assessed by epi-fluorescence conventional microscopy imaging as well as one- and two-photon excited confocal fluorescence lifetime imaging microscopy (FLIM). PVP dyes displayed low cytotoxicity, good internalization inside melanoma cells and intense fluorescence emission inside the B16-F10 murine melanoma cells, making them suitable staining agents for imaging applications.


Assuntos
Corantes Fluorescentes/química , Compostos de Piridínio/química , Coloração e Rotulagem/métodos , Animais , Corantes Fluorescentes/síntese química , Camundongos , Microscopia de Fluorescência , Fenotiazinas/química , Fótons , Compostos de Piridínio/síntese química , Solventes/química , Espectrometria de Fluorescência/métodos
5.
Molecules ; 25(19)2020 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-33020414

RESUMO

Synthesis, structural characterization and photophysical properties for a series of new trans-A2B2- and A3B-type ethynyl functionalized meso-phenothiazinyl-phenyl porphyrin derivatives are described. The new compounds displayed the characteristic porphyrin absorption spectra slightly modified by weak auxochromic effects of the substituents and fluorescence emission in the range of 651-659 nm with 11-25% quantum yields. The changes recorded in the UV-vis absorption spectra in the presence of trifluoroacetic acid (TFA) are consistent with the protonation of the two internal nitrogen atoms of the free-base porphyrin (19 nm bathochromic shift of the strong Soret band and one long wave absorption maxima situated in the range of 665-695 nm). Protonation of the phenothiazine substituents required increased amounts of TFA and produced a distinct hypsochromic shift of the long wave absorption maxima. The density functional theory (DFT) calculations of a porphyrin dication pointed out a saddle-distorted porphyrin ring as the ground-state geometry.


Assuntos
Porfirinas/química , Porfirinas/síntese química , Estrutura Molecular , Espectrofotometria Ultravioleta
6.
Int J Mol Sci ; 21(9)2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32365924

RESUMO

We report here the synthetic procedure applied for the preparation of new AB3-type and trans-A2B2 type meso-halogenophenothiazinyl-phenyl-porphyrin derivatives, their metal core complexation and their peripheral modification using Suzuki-Miyaura cross coupling reactions with various (hetero)aryl (phenothiazinyl, 7-formyl-phenothiazinyl, (9-carbazolyl)-phenyl and 4-formyl-phenyl, phenyl) boronic acid derivatives. The meso-phenothiazinyl-phenyl-porphyrin (MPP) dyes family was thus extended by a series of novel phenothiazine-bridged porphyrin-(hetero)aryl dyads characterized by UV-Vis absorption/emission properties typical to the porphyrin chromophore, slightly modulated by increasing the size of peripheral substituents. Three phenothiazine-bridged porphyrin-heteroaryl dyads with fluorescence emission above 655 nm were selected as fluorophores in red spectral region for applications in cellular staining of human ovarian tumors. In vitro experiments of cell metabolic activity displayed a moderate toxicity on human ovarian tumor cell lines (OVCAR-3, cisplatin-sensitive A2780 and cisplatin-resistant A2780cis respectively). Visualization of the stained living cells was performed both by fluorescence microscopy imaging and by fluorescence lifetime imaging under two photon excitation (TPE-FLIM), confirming their cellular uptake and the capability of staining the cell nucleus.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Fenotiazinas/química , Porfirinas/química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Feminino , Humanos , Microscopia de Fluorescência
7.
Molecules ; 25(5)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121062

RESUMO

Herein we report the synthesis of two novel series of 1,3-thiazole derivatives having a lipophilic C4-substituent on account of the increasing need for novel and versatile antifungal drugs for the treatment of resistant Candida sp.-based infections. Following their structural characterization, the anti-Candida activity was evaluated in vitro while using the broth microdilution method. Three compounds exhibited lower Minimum Inhibitory Concentration (MIC) values when compared to fluconazole, being used as the reference antifungal drug. An in silico molecular docking study was subsequently carried out in order to gain more insight into the antifungal mechanism of action, while using lanosterol-C14α-demethylase as the target enzyme. Fluorescence microscopy was employed to further investigate the cellular target of the most promising molecule, with the obtained results confirming its damaging effect towards the fungal cell membrane integrity. Finally, the distribution and the pharmacological potential in vivo of the novel thiazole derivatives was investigated through the study of their binding interaction with bovine serum albumin, while using fluorescence spectroscopy.


Assuntos
Antifúngicos , Candida/crescimento & desenvolvimento , Soroalbumina Bovina/química , Tiazóis , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Tiazóis/síntese química , Tiazóis/química , Tiazóis/farmacologia
8.
Molecules ; 24(19)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546673

RESUMO

In the context of there being a limited number of clinically approved drugs for the treatment of Candida sp.-based infections, along with the rapid development of resistance to the existing antifungals, two novel series of 4-phenyl-1,3-thiazole and 2-hydrazinyl-4-phenyl-1,3-thiazole derivatives were synthesized and tested in vitro for their anti-Candida potential. Two compounds (7a and 7e) showed promising inhibitory activity against the pathogenic C. albicans strain, exhibiting substantially lower MIC values (7.81 µg/mL and 3.9 µg/mL, respectively) as compared with the reference drug fluconazole (15.62 µg/mL). Their anti-Candida activity is also supported by molecular docking studies, using the fungal lanosterol C14α-demethylase as the target enzyme. The interaction of the most biologically active synthesized compound 7e with bovine serum albumin was investigated through fluorescence spectroscopy, and the obtained data suggested that this molecule might efficiently bind carrier proteins in vivo in order to reach the target site.


Assuntos
Antifúngicos/química , Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Simulação de Acoplamento Molecular , Soroalbumina Bovina/química , Relação Estrutura-Atividade
9.
Carbohydr Polym ; 215: 63-72, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30981371

RESUMO

Chitosan (Chit) coatings were prepared on zinc and glass substrates by dip-coating method. The coatings were impregnated with a non-toxic compound, indigo carmine (IC). The novel, eco-friendly, IC-loaded chitosan coatings were characterized morpho-structurally, and their corrosion protection behavior was investigated using potentiodynamic polarization and electrochemical impedance spectroscopy techniques. The surface properties of the coated samples were evaluated by wettability measurements. The thickness of the native chitosan layers and the stability of the impregnated layers in terms of dye release on glass substrates were studied by UV-vis spectrophotometry. The good corrosion inhibiting efficiency of the coatings (>90%) was attributed to the ionic crosslinking of the positively charged Chit with negatively charged IC. The Chit-IC coatings can be successfully used as model systems for chitosan-based coatings incorporating ionic inhibitors and in less demanding applications, such as temporary protective coatings for metals, removable on demand by scrubbing with mild acidic solutions.

10.
Int J Mol Sci ; 18(7)2017 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-28672876

RESUMO

The molecular frame of the reported series of new polyheterocyclic compounds was intended to combine the potent phenothiazine and benzothiazole pharmacophoric units. The synthetic strategy applied was based on oxidative cyclization of N-(phenothiazin-3-yl)-thioamides and it was validated by the preparation of new 2-alkyl- and 2-aryl-thiazolo[5,4-b]phenothiazine derivatives. Optical properties of the series were experimentally emphasized by UV-Vis absorption/emission spectroscopy and structural features were theoretically modelled using density functional theory (DFT). In vitro activity as antileukemic agents of thiazolo[5,4-b]phenothiazine and N-(phenothiazine-3-yl)-thioamides were comparatively evaluated using cultivated HL-60 human promyelocytic and THP-1 human monocytic leukaemia cell lines. Some representatives proved selectivity against tumour cell lines, cytotoxicity, apoptosis induction, and cellular metabolism impairment capacity. 2-Naphthyl-thiazolo[5,4-b]phenothiazine was identified as the most effective of the series by displaying against THP-1 cell lines a cytotoxicity close to cytarabine antineoplastic agent.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Fenotiazinas/química , Fenotiazinas/farmacologia , Antineoplásicos/síntese química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Fenotiazinas/síntese química , Análise Espectral , Relação Estrutura-Atividade
11.
Molecules ; 22(2)2017 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-28208774

RESUMO

Newly synthesized 2-(2-((1H-indol-5yl)methylene)-hydrazinyl)-thiazole derivatives were evaluated for their in vitro cytotoxicity on two carcinoma cell lines A2780 and HeLa. Significant cytotoxic activity for 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-methylthiazole (1) and 2-(2-((1H-indol-5-yl)methylene)hydrazinyl)-4-phenylthiazole (3), on both A2780 [IC50: 11.6 µM (1), and 12.4 µM (3)] and HeLa [IC50: 22.4 µM (1) and 19.4µM (3)] cell lines is reported. Their antioxidant potential was evaluated by spectrophotometric method, using DPPH radical or Fe (TPTZ)3+ complex, and EPR spectroscopy, therefore the compounds 1 and 3 showed remarkable antioxidant activity simultaneously with a cytotoxic effect on A2780 and HeLa cell lines. Furthermore, based on theoretical quantum chemical calculation, the present study analyzed the chemoselectivity of the hydrogen extraction from the indolyl-hydrazinil-thiazoles in reaction with free radicals.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Antineoplásicos/síntese química , Antioxidantes/síntese química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Radicais Livres/antagonistas & inibidores , Humanos , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética/métodos , Modelos Moleculares , Conformação Molecular , Tiazóis/síntese química
12.
Int J Mol Sci ; 15(12): 22059-72, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-25470024

RESUMO

New and known arylidene-hydrazinyl-thiazole derivatives have been synthesized by a convenient Hantzsch condensation. All compounds were evaluated for their in vitro cytotoxicity on two carcinoma cell lines, MDA-MB231 and HeLa. Significant antiproliferative activity for 2-(2-benzyliden-hydrazinyl)-4-methylthiazole on both MDA-MB-231 (IC50: 3.92 µg/mL) and HeLa (IC50: 11.4 µg/mL) cell lines, and for 2-[2-(4-methoxybenzylidene) hydrazinyl]-4-phenylthiazole on HeLa (IC50: 11.1 µg/mL) cell line is reported. Electrophoresis experiments showed no plasmid DNA (pTZ57R) cleavage in the presence of the investigated thiazoles.


Assuntos
Hidrazinas/síntese química , Hidrazinas/farmacologia , Tiazóis/síntese química , Tiazóis/farmacologia , Morte Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Hidrazinas/química , Concentração Inibidora 50 , Substâncias Intercalantes/farmacologia , Tiazóis/química
13.
Molecules ; 18(4): 4679-88, 2013 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-23603950

RESUMO

New aryl-hydrazinyl-1,3-selenazole and aroyl-hydrazonyl-1,3-selenazoles were synthesized via Hantzsch type condensation reactions of selenosemicarbazides with α-halogenocarbonyl derivatives, under classical versus microwave heating conditions. Excellent yields and shorter reaction times were obtained under irradiation conditions. The structures of the synthesized compounds were assigned based on spectroscopic data (FT-IR, ¹H-NMR), MS and elemental analysis. Selenazole derivatives were screened for their anti-proliferative effects against two leukemia cell lines (CCRF-CEM and HL60) and three carcinoma cell lines (MDA-MB231, HCT116 and U87MG).


Assuntos
Azóis/química , Azóis/farmacologia , Micro-Ondas , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Células HL-60 , Humanos , Concentração Inibidora 50
14.
Org Biomol Chem ; 4(23): 4375-86, 2006 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-17102884

RESUMO

A series of novel 3(5)-aryl/ferrocenyl-5(3)-phenothiazinylpyrazoles and pyrazolines were obtained by substituent-dependent regioselective condensation of the corresponding (E)-3-(2-alkyl-10H-phenothiazin-3-yl)-1-aryl/ferrocenylprop-2-en-1-one with hydrazine or methylhydrazine in acetic acid. The different propensity of the primary formed beta-hydrazino adducts to undergo competitive retro-Mannich reaction was interpreted in terms of tautomerisation equilibrium constants calculated by DFT using a solvent model. The regioselectivity of the cyclisation reactions with methylhydrazine and the substituent-dependent redox properties of pyrazolines were also rationalized by comparative DFT calculations performed for simplified model molecules. On the effect of ultrasound-promoted oxidation with copper(II)nitrate phenothiazine-containing pyrazolines, enones and oxo-compounds were selectively transformed into sulfoxides. Only one sulfoxide enone was partially converted into an oxirane derivative. The structure of the novel products was determined by IR and NMR spectroscopy including COSY, HSQC, HMBC and DNOE measurements.


Assuntos
Cobre/química , Hidrazinas/química , Nitratos/química , Fenotiazinas/química , Ciclização , Espectroscopia de Ressonância Magnética , Oxirredução , Fenotiazinas/síntese química , Pirazolonas/química , Sonicação , Espectrofotometria Infravermelho
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...