RESUMO
Novel fluorescent quinoxaline and quinoline hydroperoxides were shown to perform dual role as both fluorophores for cell imaging and photoinduced DNA cleaving agents. Photophysical studies of newly synthesized quinoxaline and quinoline hydroperoxides showed that they all exhibited moderate to good fluorescence. Photolysis of quinoxaline and quinoline hydroperoxides in acetonitrile using UV light above 350nm resulted in the formation of corresponding ester compounds via γ-hydrogen abstraction by excited carbonyl chromophore. Single strand DNA cleavage was achieved on irradiation of newly synthesized hydroperoxides by UV light (⩾350nm). Both hydroxyl radicals and singlet oxygen were identified as reactive oxygen species (ROS) responsible for the DNA cleavage. Further, we showed quinoline hydroperoxide binds to ct-DNA via intercalative mode. In vitro biological studies revealed that quinoline hydroperoxide has good biocompatibility, cellular uptake property and cell imaging ability. Finally, we showed that quinoline hydroperoxide can permeate into cells efficiently and may cause cytotoxicity upon irradiation by UV light.
Assuntos
Corantes Fluorescentes , Peróxidos , Quinolinas , Quinoxalinas , Sobrevivência Celular/efeitos dos fármacos , DNA/química , DNA/metabolismo , Clivagem do DNA , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacologia , Células HeLa , Humanos , Radical Hidroxila/química , Simulação de Acoplamento Molecular , Peróxidos/química , Peróxidos/farmacologia , Peróxidos/efeitos da radiação , Fotólise , Quinolinas/química , Quinolinas/farmacologia , Quinolinas/efeitos da radiação , Quinoxalinas/química , Quinoxalinas/farmacologia , Quinoxalinas/efeitos da radiação , Oxigênio Singlete/química , Espectrometria de Fluorescência , Raios UltravioletaRESUMO
Light is an exquisite reagent for controlling the activity of biological systems, often offering improved temporal and spatial resolution over strictly genetic, biochemical, or pharmacological manipulations. This chapter describes a general approach for developing small molecules that, upon irradiation with light, may be used to rapidly inactivate targeted proteins expressed on the surfaces of cells. Highlighted is ANQX, a photoreactive AMPA receptor antagonist developed to irreversibly inactivate a subtype of glutamate-gated ion channels natively expressed on neurons.
Assuntos
Receptores de AMPA/antagonistas & inibidores , Animais , Azidas/química , Azidas/efeitos da radiação , Benzofenonas/química , Benzofenonas/efeitos da radiação , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/efeitos da radiação , Desenho de Fármacos , Antagonistas de Aminoácidos Excitatórios/química , Antagonistas de Aminoácidos Excitatórios/efeitos da radiação , Luz , Processos Fotoquímicos , Quinoxalinas/química , Quinoxalinas/efeitos da radiaçãoRESUMO
A simple colorimetric and fluorescent anion chemosensor based on amide moieties, 6-nitro-1,4-dihydroquinoxaline-2,3-dione has been designed, synthesized and characterized by (1)H NMR, ESI-MS and elemental analyses. The strong basic anions such as F(-) and AcO(-) resulted in significant decrease in fluorescent emission intensity of the compound 1, accompanied synchronously with a dramatic color change from colorless to deep yellow in organic medium. (1)H NMR titration experiments shed light on the nature of the interactions between 1 and the anions.
Assuntos
Amidas/química , Ânions/química , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/química , Quinoxalinas/química , Acetatos/química , Amidas/síntese química , Amidas/efeitos da radiação , Colorimetria , Corantes Fluorescentes/síntese química , Corantes Fluorescentes/efeitos da radiação , Fluoretos/química , Quinoxalinas/síntese química , Quinoxalinas/efeitos da radiação , Espectrofotometria UltravioletaRESUMO
We synthesize quinoxalines, catalyzed by manganese(IV) dioxide, from a variety of alpha-hydroxyketones followed by trapping with aromatic or aliphatic 1,2-diamines without using a solvent, within one minute under microwave irradiation.
Assuntos
Compostos de Manganês/química , Compostos de Manganês/efeitos da radiação , Micro-Ondas , Óxidos/química , Óxidos/efeitos da radiação , Quinoxalinas/síntese química , Quinoxalinas/efeitos da radiação , Catálise , Estrutura Molecular , Quinoxalinas/química , EstereoisomerismoRESUMO
An amphiphilic styrylquinoxaline derivative, 3-(4-(hexadecyloxy)styryl)quinoxalin-2(1H)-one (SQC16), was newly synthesized to investigate their photochemical and gas responsive properties in organized molecular films. It was observed that SQC16 can spread as a monolayer on the subphases with various pH values and be subsequently transferred onto solid substrates. While SQC16 showed predominantly reversible trans-cis photoisomerization in methanol solution, it showed both photoisomerization and photodimerization in Langmuir-Blodgett (LB) films. Photodimerization was only observed in the LB film due to the face-to-face arrangement of the functional headgroup in the LB film, and the process was irreversible. In addition, the LB film showed acidichromism, i.e., when the film was exposed to HCl gas its color changed from yellow to red, and the color could be recovered after exposure to NH(3) gas. The process was reversible and could be repeated many times. An interesting surface morphology of the SQC16 LB film was revealed. It was observed that SQC16 can form nanowire architecture in the transferred one-layer LB film. This morphology can be changed upon photoirradiation or in gas reactions. Through the atomic force microscopy measurements it was suggested that the photodimerization predominantly occurred from the nanowire structures, while during the acidichromism the reaction occurred preferentially in the flat region. X-ray diffraction studies revealed that while layer distance showed a slight change for the LB film during acidichromism and photoreaction, the layer structure of SQC16 LB film was retained.
Assuntos
Membranas Artificiais , Nanoestruturas/química , Nanoestruturas/efeitos da radiação , Quinoxalinas/química , Quinoxalinas/efeitos da radiação , Raios Ultravioleta , Microscopia de Força Atômica/métodos , Estrutura Molecular , Tamanho da Partícula , Fotoquímica , Quinoxalinas/síntese química , Sensibilidade e Especificidade , Espectrofotometria Ultravioleta/métodos , Propriedades de SuperfícieRESUMO
A range of lipo- and hydrophilic derivatives of the new class of octaalkynyl tetra-[6,7]-quinoxalinoporphyrazines (TQuiPors), analogues of the naphthalocyanines, were prepared in two steps starting from functionalised hexa-1,5-diyne-3,4-diones. Divalent zinc and magnesium ions were introduced into the macrocyclic core. Whereas the triisopropylsilyl-, 3,5-di-tert-butylphenyl- and 4-triisopropylsilyloxyphenyl-terminated acetylenic TQuiPors are lipophilic and hence soluble in standard organic solvents, a polyethylene glycol-substituted derivative was found to dissolve in DMSO as well as in ethanol/water mixtures. The new chromophores are characterised by intense UV/Vis/NIR absorptions, most notably by bands at 770 nm with extinction coefficients exceeding 500 000 M(-1) cm(-1). With a view to possible photodynamic therapy applications, the potency of the chromophores to sensitise the formation of singlet oxygen was examined, both qualitatively using a 1,3-diphenylisobenzofuran assay, and quantitatively by the determination of the singlet oxygen quantum yields. It was found that all TQuiPors produce singlet oxygen when irradiated in the presence of air. In particular, the octaalkynyl Zn-TQuiPor generates singlet oxygen with a quantum yield of 56 %, thereby rivalling, and, in conjunction with its absorption profile, even exceeding the standards set by established PDT agents. The photostabilities of the TQuiPors were assessed and generally found to be satisfactory, but dependent on the solvent and the wavelength of the incident light.
Assuntos
Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/síntese química , Porfirinas/síntese química , Quinoxalinas/síntese química , Indóis , Isoindóis , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Porfirinas/química , Porfirinas/efeitos da radiação , Quinoxalinas/química , Quinoxalinas/efeitos da radiação , Oxigênio Singlete/química , Solubilidade , Análise Espectral , Relação Estrutura-AtividadeRESUMO
Quindoxin (quinoxaline-1,4-dioxide), a former 'growth promoter' used in animal husbandry, has been taken from the market because of its photoallergic properties. Nowadays its derivatives olaquindox, carbadox and cyadox are frequently applied for the same purpose. Recent reports show that olaquindox too, can induce photoallergic skin reactions in stockmen. From the present investigation it appeared that all compounds mentioned, form a reactive oxaziridine upon exposure to light, just like many other imino-N-oxides. Photoreactivity with protein, which is considered as an important condition for a compound to be a potential photoallergen, was also studied. Quindoxin and olaquindox proved to meet this condition, as was expected. But carbadox and cyadox also react and were shown to be even more reactive towards human serum albumin.
Assuntos
Carbadox/metabolismo , Transtornos de Fotossensibilidade/etiologia , Proteínas/metabolismo , Quinoxalinas/metabolismo , Animais , Antibacterianos/metabolismo , Antibacterianos/efeitos da radiação , Carbadox/efeitos da radiação , Carbadox/toxicidade , Fenômenos Químicos , Química , Humanos , Compostos Organofosforados/farmacologia , Fotoquímica , Quinoxalinas/efeitos da radiação , Quinoxalinas/toxicidade , Albumina Sérica/metabolismo , Raios UltravioletaRESUMO
Quindoxin (quinoxaline di-N-oxide) is a photosensitizer capable of producing photocontact dermatitis. The study of a group of seven affected subjects has provided evidence of persistent light reaction and "photoallergy", most probably to the parent substance and not to any photoproduct or contaminant. Clinical and photobiological similarities to the photosensitivity dermatitis and actinic reticuloid syndrome were demonstrated.