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1.
Int J Mol Sci ; 21(8)2020 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-32316355

RESUMO

A class of amphiphilic photosensitizers for photodynamic therapy (PDT) was developed. Sulfonate esters of modified porphyrins bearing-F substituents in the ortho positions of the phenyl rings have adequate properties for PDT, including absorption in the red, increased cellular uptake, favorable intracellular localization, low cytotoxicity, and high phototoxicity against A549 (human lung adenocarcinoma) and CT26 (murine colon carcinoma) cells. Moreover, the role of type I and type II photochemical processes was assessed by fluorescent probes specific for various reactive oxygen species (ROS). The photodynamic effect is improved not only by enhanced cellular uptake but also by the high generation of both singlet oxygen and oxygen-centered radicals. All of the presented results support the idea that the rational design of photosensitizers for PDT can be further improved by better understanding the determinants affecting its therapeutic efficiency and explain how smart structural modifications can make them suitable photosensitizers for application in PDT.


Assuntos
Fármacos Fotossensibilizantes/química , Porfirinas/química , Espécies Reativas de Oxigênio/metabolismo , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Corantes Fluorescentes/química , Halogenação , Humanos , Luz , Camundongos , Microscopia Confocal , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Fotoquimioterapia , Fármacos Fotossensibilizantes/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Porfirinas/metabolismo , Porfirinas/farmacologia , Porfirinas/uso terapêutico , Espécies Reativas de Oxigênio/química , Oxigênio Singlete/química , Oxigênio Singlete/metabolismo
2.
Dalton Trans ; 48(10): 3249-3262, 2019 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-30776044

RESUMO

For the development of redox responsive MRI probes based on the MnIII/MnII couple, stable complexation of both reduced and oxidized forms of the metal ion and appropriate tuning of the redox potential in the biologically relevant range are key elements. The water soluble fluorinated Mn-porphyrin derivative Mn-3 satisfies both requirements. In aqueous solutions, it can reversibly switch between MnIII/MnII oxidation states. In the presence of ascorbic acid or ß-mercaptoethanol, the MnIII form undergoes reduction, which is slowly but fully reversed in the presence of air oxygen. A UV-Vis kinetic study of MnIII/MnII reduction under oxygen-free conditions yielded second-order rate constants, k2, of 46.1 M-1 s-1 and 13.8 M-1 s-1 for the reaction with ascorbic acid and ß-mercaptoethanol, respectively. This could correspond, in the absence of oxygen, to a half-life of a few minutes in blood plasma and a few seconds in circulating immune cells where ascorbic acid reaches 20-40 µM and a few mM concentrations, respectively. In contrast to expectations based on the redox potential, reduction with glutathione or cysteine does not occur. It is prevented by the coordination of the glutathione carboxylate group(s) to MnIII in the axial position, as was evidenced by NMR data. Therefore, MnIII-3 acts as an ascorbate specific turn-on MRI probe, which in turn can be re-oxidized by oxygen. The relaxivity increase from the oxidized to the reduced form is considerably improved at medium frequencies (up to 80 MHz) with respect to the previously studied Mn-TPPS4 analogues; at 20 MHz, it amounts to 150%. No in vitro cytotoxicity is detectable for Mn-3 in the typical MRI concentration range. Finally, 19F NMR resonances of MnIII-3 are relatively sharp which could open further opportunities to exploit such complexes as paramagnetic 19F NMR probes.

3.
Molecules ; 24(1)2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30586854

RESUMO

In the present study, we developed a green epoxidation approach for the synthesis of the diastereomers of (-)-isopulegol benzyl ether epoxide using molecular oxygen as the oxidant and a hybrid manganese(III)-porphyrin magnetic reusable nanocomposite as the catalyst. High activity, selectivity, and stability were obtained, with up to four recycling cycles without the loss of activity and selectivity for epoxide. The anticancer effect of the newly synthesized isopulegol epoxide diastereomers was evaluated on a human osteosarcoma cell line (MG-63); both diastereomers showed similar in vitro potency. The measured IC50 values were significantly lower than those reported for other monoterpene analogues, rendering these epoxide isomers as promising anti-tumor agents against low prognosis osteosarcoma.


Assuntos
Antineoplásicos/farmacologia , Biomimética , Fenômenos Magnéticos , Metaloporfirinas/química , Nanocompostos/química , Osteossarcoma/patologia , Antineoplásicos/síntese química , Antineoplásicos/química , Varredura Diferencial de Calorimetria , Catálise , Linhagem Celular Tumoral , Monoterpenos Cicloexânicos , Compostos de Epóxi/síntese química , Compostos de Epóxi/química , Humanos , Manganês/química , Nanocompostos/ultraestrutura , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Estereoisomerismo , Terpenos/síntese química , Terpenos/química , Terpenos/farmacologia , Termogravimetria
4.
Molecules ; 22(5)2017 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-28475140

RESUMO

Herein we report the synthesis of unsymmetrical meso-aryl substituted porphyrins, using NaY zeolite as an inorganic acid catalyst. A comparative study between this method and the several synthetic strategies available in the literature was carried out. Our method presented a better, more cost-efficient rationale and displayed a significantly lower environmental impact. Furthermore, it was possible to verify the scalability of the process as well as the reutilization of the inorganic catalyst NaY (up to 6 times) without significant yield decrease. In addition, this method was applied to the synthesis of several other unsymmetrical porphyrins, from a low melting point porphyrin to mono-carboxylated halogenated unsymmetrical porphyrins, in yields higher than those found in the literature. Additionally, for the first time, two acetamide functionalized halogenated porphyrins were prepared in high yields. This methodology opens the way to the preparation of high yielding functionalized porphyrins, which can be easily immobilized for a variety of applications, either in catalysis or in biomedicine.


Assuntos
Análise Custo-Benefício , Porfirinas/síntese química , Sódio/química , Ítrio/química , Zeolitas/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Catálise , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
5.
Dalton Trans ; 45(41): 16211-16220, 2016 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-27722477

RESUMO

Herein, the synthesis and characterisation of magnetic iron oxide-porphyrin hybrids, constituted of iron-oxide magnetic nanoparticles covalently linked to an unsymmetrically substituted meso-aryl porphyrin, are described. The methodology features for the preparation of the key unsymmetrically substituted meso-aryl porphyrin synthons are discussed, with emphasis on sustainability and in economical terms. The "NaY method" herein reported allows large scale and economical preparation, which are demonstrated by its reusability and at least two-fold yields, when compared with classical porphyrin synthetic methods and also presents a much better cost-efficiency rationale and lower environmental impact. Upon covalent linking to iron-oxide magnetic nanoparticles, the new hybrids are fully characterised by thermogravimetry/differential scanning calorimetry, transmission electron microscopy and infrared spectroscopy and their photophysical properties were measured, which demonstrate that the presence of the magnetic nanoparticle counterparts does not affect these properties, thus allowing the materials to keep the photophysical features imparted by their porphyrin counterparts.

6.
J Med Chem ; 59(10): 4688-96, 2016 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-27070884

RESUMO

Diamagnetic metal complexes of phthalocyanines with n-butoxyl groups in all the α-benzo positions of the macrocycle skeleton, MPc(OBu)8, have strong near-infrared absorptions and intense fluorescences that are Stokes shifted by more than 15 nm. Interestingly, the silicon complex 6 is also remarkably photostable and nontoxic. The use of 6 in the fluorescence imaging of BALB/c mice bearing a 4T1-luc2 tumor in the mammary fat pad unambiguously revealed the presence of the tumor when it was only 1 mm in diameter and was not visible with the naked eye. Compound 6 has an intrinsic ability to accumulate in the tumor, adequate spectroscopic properties, and excellent stability to function as a NIR fluorescent label in the early detection of tumors.


Assuntos
Fluorescência , Indóis/química , Neoplasias Mamárias Animais/diagnóstico por imagem , Imagem Óptica , Compostos Organometálicos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Isoindóis , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Compostos Organometálicos/síntese química , Relação Estrutura-Atividade
7.
J Inorg Biochem ; 154: 50-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26583704

RESUMO

Water soluble phthalocyanines bearing either four PEG500 or four choline substituents in the macrocyclic structure, as well as their Zn(II) and Mn(III) complexes were synthesized. The metal-free and Zn(II) complexes present relatively high fluorescence quantum yields (up to 0.30), while the Mn(III) complexes show no fluorescence as a consequence of rapid non-radiative deactivation of the Mn(III) phthalocyanine excited states through low-lying metal based or charge-transfer states. The effect of DMSO on the aggregation of the phthalocyanines was studied. It was not possible to obtain the Mn(II) complexes by reduction of the corresponding Mn(III) complexes due to the presence of electron donating substituents at the periphery of the phthalocyanines. The (1)H NMRD plots of the PEG500 and choline substituted Mn(III)-phthalocyanine complexes are typical of self-aggregated Mn(III) systems with r1 relaxivities of 4.0 and 5.7mM(-1)s(-1) at 20MHz and 25°C. The Mn(III)-phthalocyanine-PEG4 complex shows no significant cytotoxicity to HeLa cell cultures after 2h of incubation up to 2mM concentration. After 24h of cell exposure to the compound, significant toxicity was observed for all the concentrations tested with IC50 of 1.105mM.


Assuntos
Colina/análogos & derivados , Colina/síntese química , Indóis/síntese química , Polietilenoglicóis/síntese química , Sobrevivência Celular/efeitos dos fármacos , Colina/toxicidade , Células HeLa , Humanos , Indóis/toxicidade , Concentração Inibidora 50 , Isoindóis , Imagem Molecular , Polietilenoglicóis/toxicidade
8.
ChemSusChem ; 7(10): 2821-4, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25111181

RESUMO

Water, under microwave irradiation and at a temperature of 473 K, reaches pressures above 16 bar, being capable to act as catalyst, without the use of organic solvents and oxidants, for meso-substituted porphyrin synthesis. Sustainability of the reaction is proved by E Factor=35 and EcoScale value of 50.5, the highest so far obtained for porphyrin synthesis. Methodology's wide versatility is clearly demonstrated by the good yields obtained for both aryl and alkyl substituted porphyrins. These reaction conditions represent a huge development, not only by using very high concentrations, minimizing organic solvent usage, but also by eradicating toxic expensive solvents and oxidants.


Assuntos
Aldeídos/química , Porfirinas/síntese química , Pirróis/química , Água/química , Catálise , Química Verde/métodos , Espectroscopia de Ressonância Magnética , Micro-Ondas
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