RESUMEN
Presented in this paper is a study on the photodegradation of two widely used neonicotinoid insecticides clothianidin and thiamethoxam in three soils and in solid phase. The effects of light with differing wavelengths were examined using the natural sunlight and single ultraviolet A (UVA) and ultraviolet B (UVB) light sources. The results indicated that UVB played a key role in the photodegradation of clothianidin and thiamethoxam while the effects of visible and UVA lights were negligible. The degradations of clothianidin and thiamethoxam under all the light sources followed the first-order kinetics, and the half-lives of clothianidin and thiamethoxam in the three soils under the sunlight ranged from 97 to 112 h and 88 to 103 h, respectively. When clothianidin and thiamethoxam were directly exposed to the sunlight without soil, the degradation rates were remarkably higher with half-lives being 13 and 10 h, respectively. Therefore, the insecticides fallen on the surface of soils would be degraded under sunlight much faster than those that enter the soils. The examination of the degradation products revealed four compounds from the photodegradation of clothianidin and three from thiamethoxam, and clothianidin was one of the photodegradation products of thiamethoxam.
Asunto(s)
Restauración y Remediación Ambiental , Guanidinas/química , Insecticidas/química , Neonicotinoides/química , Contaminantes del Suelo/química , Tiametoxam/química , Tiazoles/química , Agricultura , Guanidinas/efectos de la radiación , Neonicotinoides/efectos de la radiación , Fotólisis , Suelo , Contaminantes del Suelo/efectos de la radiación , Luz Solar , Tiametoxam/efectos de la radiación , Tiazoles/efectos de la radiación , Rayos UltravioletaRESUMEN
The ideal fluorescent probe for live-cell imaging is bright and non-cytotoxic and can be delivered easily into the living cells in an efficient manner. The design of synthetic fluorophores having all three of these properties, however, has proved to be challenging. Here, we introduce a simple, yet effective, strategy based on well-established chemistry for designing a new class of fluorescent probes for live-cell imaging. A box-like hybrid cyclophane, namely ExTzBox·4X (6·4X, X = PF6-, Cl-), has been synthesized by connecting an extended viologen (ExBIPY) and a dipyridyl thiazolothiazole (TzBIPY) unit in an end-to-end fashion with two p-xylylene linkers. Photophysical studies show that 6·4Cl has a quantum yield ΦF = 1.00. Furthermore, unlike its ExBIPY2+ and TzBIPY2+ building units, 6·4Cl is non-cytotoxic to RAW 264.7 macrophages, even with a loading concentration as high as 100 µM, presumably on account of its rigid box-like structure which prevents its intercalation into DNA and may inhibit other interactions with it. After gaining an understanding of the toxicity profile of 6·4Cl, we employed it in live-cell imaging. Confocal microscopy has demonstrated that 64+ is taken up by the RAW 264.7 macrophages, allowing the cells to glow brightly with blue laser excitation, without any hint of photobleaching or disruption of normal cell behavior under the imaging conditions. By contrast, the acyclic reference compound Me2TzBIPY·2Cl (4·2Cl) shows very little fluorescence inside the cells, which is quenched completely under the same imaging conditions. In vitro cell investigations underscore the significance of using highly fluorescent box-like rigid cyclophanes for live-cell imaging.
Asunto(s)
Colorantes Fluorescentes/química , Compuestos Macrocíclicos/química , Compuestos de Piridinio/química , Tiazoles/química , Animales , Fluorescencia , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Colorantes Fluorescentes/toxicidad , Luz , Compuestos Macrocíclicos/síntesis química , Compuestos Macrocíclicos/efectos de la radiación , Compuestos Macrocíclicos/toxicidad , Ratones , Microscopía Confocal/métodos , Modelos Químicos , Compuestos de Piridinio/síntesis química , Compuestos de Piridinio/efectos de la radiación , Compuestos de Piridinio/toxicidad , Teoría Cuántica , Células RAW 264.7 , Tiazoles/síntesis química , Tiazoles/efectos de la radiación , Tiazoles/toxicidadRESUMEN
Retinal prosthesis or artificial retina is a promising modality of treatment for outer retinal degeneration, caused by primary and secondary loss of photoreceptor cells, in hereditary retinal dystrophy and age-related macular degeneration, respectively. Okayama University-type retinal prosthesis (OUReP) is a photoelectric dye-coupled polyethylene film which generates electric potential in response to light and stimulates nearby neurons. The dye-coupled films were implanted by vitreous surgery in the subretinal space of monkey eyes with macular degeneration which had been induced by cobalt chloride injection from the scleral side. A pilot 1-month observation study involved 6 monkeys and a pivotal 6-month observation study involved 8 monkeys. Of 8 monkeys in 6-month group, 3 monkeys underwent dye-coupled film removal at 5 months and were observed further for 1 month. The amplitude of visual evoked potential which had been reduced by macular degeneration did recover at 1 month after film implantation and maintained the level at 6 months. Optical coherence tomography showed no retinal detachment, and full-field electroretinograms maintained a-wave and b-wave amplitudes, indicative of no retinal toxicity. Pathological examinations after 6-month implantation showed structural integrity of the inner retinal layer in close apposition to dye-coupled films. The implanted films which were removed by vitrectomy 5 months later showed light-evoked surface electric potentials by scanning Kelvin probe measurement. The photoelectric dye-coupled film (OUReP), which serves as a light-receiver and a displacement current generator in the subretinal space of the eye, has a potential for recovering vision in diseases with photoreceptor cell loss, such as retinitis pigmentosa and age-related macular degeneration.
Asunto(s)
Potenciales Evocados Visuales , Degeneración Macular/cirugía , Implantación de Prótesis/instrumentación , Retina/cirugía , Prótesis Visuales , Compuestos de Anilina/química , Compuestos de Anilina/efectos de la radiación , Animales , Modelos Animales de Enfermedad , Estudios de Factibilidad , Luz , Macaca fascicularis , Degeneración Macular/patología , Degeneración Macular/fisiopatología , Proyectos Piloto , Polietileno/química , Diseño de Prótesis , Recuperación de la Función , Retina/patología , Retina/fisiopatología , Propiedades de Superficie , Tiazoles/química , Tiazoles/efectos de la radiación , Factores de TiempoRESUMEN
Environmental presence and retention of commonly used neonicotinoid insecticides such as dinotefuran (DNT), imidacloprid (IMD), and thiamethoxam (THM) are a cause for concern and prevention because of their potential toxicity to nontarget species. In the present study the kinetics of the photodegradation of these insecticides were investigated in water and soil compartments under natural light conditions. The results suggest that these insecticides are fairly unstable in both aqueous and soil environments when exposed to natural sunlight. All 3 insecticides exhibit strong first-order degradation rate kinetics in the aqueous phase, with rate constants kDNT , kIMD , and kTHM of 0.20 h(-1) , 0.30 h(-1) , and 0.18 h(-1) , respectively. However, in the soil phase, the modeled photodegradation kinetics appear to be biphasic, with optimal rate constants k1DNT and k2DNT of 0.0198 h(-1) and 0.0022 h(-1) and k1THM and k2THM of 0.0053 h(-1) and 0.0014 h(-1) , respectively. Differentially, in the soil phase, imidacloprid appears to follow the first-order rate kinetics with a kIMD of 0.0013 h(-1) . These results indicate that all 3 neonicotinoids are photodegradable, with higher degradation rates in aqueous environments relative to soil environments. In addition, soil-encapsulated imidacloprid appears to degrade slowly compared with dinotefuran and thiamethoxam and does not emulate the faster degradation rates observed in the aqueous phase. Environ Toxicol Chem 2016;35:1718-1726. © 2015 SETAC.
Asunto(s)
Guanidinas/análisis , Imidazoles/análisis , Modelos Teóricos , Nitrocompuestos/análisis , Oxazinas/análisis , Fotólisis , Contaminantes del Suelo/análisis , Tiazoles/análisis , Contaminantes Químicos del Agua/análisis , Guanidinas/efectos de la radiación , Imidazoles/efectos de la radiación , Cinética , Neonicotinoides , Nitrocompuestos/efectos de la radiación , Oxazinas/efectos de la radiación , Suelo/química , Contaminantes del Suelo/química , Tiametoxam , Tiazoles/efectos de la radiación , Rayos Ultravioleta , Contaminantes Químicos del Agua/efectos de la radiaciónRESUMEN
Thioflavin T (ThT) is a fluorescent dye able to enhance significantly its fluorescence quantum yield upon binding to protein amyloids. ThT assay is widely used to detect and quantify amyloids in a variety of conditions, including solutions with different pH levels. In the present work, the effect of acidic and basic pH on the conformation of the ThT molecule and its absorption and fluorescence properties was studied. The results show that both acidic and basic pH decrease significantly the intensity of ThT absorption in the visible region and fluorescence emission intensity. Low pHs induce an immediate "all-or-nothing" decrease in the ThT signal, while in alkaline solutions the ThT signal decreases gradually over time. pH-induced signal quenching is less in the presence of glycerol or protein aggregates. Two different mechanisms are responsible for the ThT signal quenching-the ThT hydroxylation at basic pH and protonation of the nitrogen atom of the dimethylamino group at acidic pH. ThT assays should be carefully carried out at basic or acidic pH as strong pH dependence of ThT could be responsible for misinterpretation and false positive/negative experimental results. The potential unsuitability of ThT as a probe in solutions with high pH (>9) has been shown.
Asunto(s)
Absorción de Radiación , Colorantes Fluorescentes/química , Tiazoles/química , Benzotiazoles , Fluorescencia , Colorantes Fluorescentes/efectos de la radiación , Concentración de Iones de Hidrógeno , Tiazoles/efectos de la radiación , Rayos UltravioletaRESUMEN
A selective, accurate, precise and robust stability indicating liquid chromatography assay method was developed for the monitoring of a novel antipsychotic drug, lurasidone, in the presence of its degradation products (DPs). Also, we investigated degradation behavior of the drug under various stressed conditions such as hydrolytic (acidic, basic and neutral), oxidation, photolytic and thermal. The drug was found to be degraded under base hydrolytic and oxidative conditions, while it was stable in acid and neutral hydrolytic, photolytic and thermal conditions. The method showed adequate separation of lurasidone and its DPs on Xterra C18 (150 mm × 4.6 mm i.d., 3.5 µm) column using 20 mM ammonium formate (pH 3.0): acetonitrile as a mobile phase in gradient elution mode at a flow rate of 0.6 mL/min. This method was extended to liquid chromatography electrospray ionization quadrupole time-of-flight mass spectrometry (LC/ESI/QTOF/MS/MS) for structural characterization of DPs. A total of five DPs were characterized by LC/ESI/QTOF/MS/MS studies. Most probable mechanisms for the formation of DPs were proposed. The developed method was validated in terms of specificity, linearity, accuracy, precision, and robustness as per International Conference on Harmonization Guideline Q2 (R1).
Asunto(s)
Álcalis/química , Cromatografía Líquida de Alta Presión/métodos , Isoindoles/análisis , Psicotrópicos/análisis , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Tiazoles/análisis , Estabilidad de Medicamentos , Calor , Hidrólisis , Isoindoles/química , Isoindoles/efectos de la radiación , Clorhidrato de Lurasidona , Oxidación-Reducción , Fotólisis , Psicotrópicos/química , Psicotrópicos/efectos de la radiación , Tiazoles/química , Tiazoles/efectos de la radiación , Rayos UltravioletaRESUMEN
Here, we investigated the degradation kinetics of butenolide, a promising antifouling compound, under various environmental conditions. The active ingredient of the commercial antifoulant SeaNine 211, 4,5-dichloro-2-n-octyl-4-isothiazolin-3-one (DCOIT), was used as positive control. The results showed that the degradation rate increased with increasing temperature. Half-lives of butenolide at 4 °C, 25 °C and 40 °C were>64 d, 30.5 d and 3.9 d, respectively. Similar half-lives were recorded for DCOIT: >64 d at 4 °C, 27.9 d at 25 °C and 4.5d at 40 °C. Exposure to sunlight accelerated the degradation of both butenolide and DCOIT. The photolysis half-lives of butenolide and DCOIT were 5.7 d and 6.8 d, respectively, compared with 9.7 d and 14.4 d for the dark control. Biodegradation led to the fastest rate of butenolide removal from natural seawater, with a half-life of 0.5 d, while no obvious degradation was observed for DCOIT after incubation for 4 d. The biodegradative ability of natural seawater for butenolide was attributed mainly to marine bacteria. During the degradation of butenolide and DCOIT, a gradual decrease in antifouling activity was observed, as indicated by the increased settlement percentage of cypris larvae from barnacle Balanus amphitrite. Besides, increased cell growth of marine diatom Skeletonema costatum demonstrated that the toxicity of seawater decreased gradually without generation of more toxic by-products. Overall, rapid degradation of butenolide in natural seawater supported its claim as a promising candidate for commercial antifouling industry.
Asunto(s)
4-Butirolactona/análogos & derivados , 4-Butirolactona/metabolismo , 4-Butirolactona/efectos de la radiación , 4-Butirolactona/toxicidad , Animales , Bacterias/metabolismo , Biodegradación Ambiental , Diatomeas/efectos de los fármacos , Diatomeas/crecimiento & desarrollo , Semivida , Cinética , Larva/efectos de los fármacos , Fotólisis , Agua de Mar/microbiología , Tiazoles/metabolismo , Tiazoles/efectos de la radiación , Tiazoles/toxicidad , Thoracica/efectos de los fármacos , Microbiología del AguaRESUMEN
This research focused on photocatalytic degradation of imidacloprid, thiamethoxam and clothianidin employing a tailor-made photoreactor with six polychromatic fluorescent UVA (broad maximum at 355 nm) lamps and immobilised titanium dioxide (TiO(2)) on glass slides. The disappearance was followed by high pressure liquid chromatography (HPLC-DAD) analyses, wherein the efficiency of mineralization was monitored by measurements of total organic carbon (TOC). Within 2h of photocatalysis, all three neonicotinoids were degraded following first order kinetics with rate constants k=0.035 ± 0.001 min(-1) for imidacloprid, k=0.019 ± 0.001 min(-1) for thiamethoxam and k=0.021 ± 0.000 min(-1) for clothianidin. However, the rate of mineralization was low, i.e. 19.1 ± 0.2% for imidacloprid, 14.4 ± 2.9% for thiamethoxam and 14.1 ± 0.4% for clothianidin. This indicates that several transformation products were formed instead. Some of them were observed within HPLC-DAD analyses and structures were proposed according to the liquid chromatography-electro spray ionization tandem mass spectrometry analyses (LC-ESI-MS/MS). The formation of clothianidin, as thiamethoxam transformation product, was reported for the first time.
Asunto(s)
Guanidinas/química , Imidazoles/química , Insecticidas/química , Nitrocompuestos/química , Oxazinas/química , Tiazoles/química , Catálisis , Cromatografía Líquida de Alta Presión , Cromatografía Liquida , Guanidinas/efectos de la radiación , Imidazoles/efectos de la radiación , Insecticidas/efectos de la radiación , Cinética , Neonicotinoides , Nitrocompuestos/efectos de la radiación , Oxazinas/efectos de la radiación , Fotólisis , Espectrometría de Masas en Tándem , Tiametoxam , Tiazoles/efectos de la radiación , TitanioRESUMEN
Inclusion complexes of ziprasidone with several ß-cyclodextrins [ß-CDs; sulfobutylether-ß-cyclodextrins (SBEßCD), hydroxypropyl-ß-cyclodextrins (HPßCD), methyl-ß-cyclodextrins (MßCD), and carboxyethyl-ß-cyclodextrins (CEßCD)] were prepared and solution stability was evaluated at elevated temperature. Solid-state stability was assessed by subjecting various CD complexes of ziprasidone, spray-dried dispersion (SDD), partially crystalline ziprasidone-SBEßCD salts, and the physical mixture of ziprasidone-SBEßCD to γ-irradiation. Degradant I was formed by oxidation of ziprasidone, which upon aldol condensation with ziprasidone formed degradant II in both solution and solid states. In the solution state, CD complexes with electron-donating side chains, such as SBEßCD and CEßCD, produced the highest oxidative degradation followed by HPßCD with 6, 3, and 4 degrees of substitution. In the solid state, crystalline drug substance and physical mixture of crystalline drug-SBEßCD showed very little to no degradation. In contrast, amorphous ßCD, MßCD, CEßCD, and SBEßCD complexes as well as the amorphous SDD exhibited greatest extent of oxidative degradation. Results suggest that electron-donating side chains of the derivatized CD interact with transition state of the oxidation reaction and catalyze drug degradation in solution, However, higher mobility in the amorphous state of CD-drug complexes promoted chemical instability of ziprasidone under accelerated conditions irrespective of the chemical nature of the side chain on CD.
Asunto(s)
Antipsicóticos/química , Excipientes/química , Piperazinas/química , Tiazoles/química , beta-Ciclodextrinas/química , 2-Hidroxipropil-beta-Ciclodextrina , Antipsicóticos/efectos de la radiación , Química Farmacéutica , Cromatografía Líquida de Alta Presión , Cristalización , Cristalografía por Rayos X , Composición de Medicamentos , Estabilidad de Medicamentos , Rayos gamma , Calor , Concentración de Iones de Hidrógeno , Cinética , Espectroscopía de Resonancia Magnética , Oxidación-Reducción , Piperazinas/efectos de la radiación , Difracción de Polvo , Solubilidad , Tecnología Farmacéutica/métodos , Tiazoles/efectos de la radiaciónRESUMEN
Photodegradation of the insecticide thiamethoxam (1), 3-[(2-chloro-5-thiazolyl)methyl]tetrahydro-5-methyl-N-nitro-4H-1,3,5-oxadiazin-4-imine, in an aqueous medium was monitored by electrospray ionization mass spectrometry in the positive ion mode, ESI(+)-MS. An aqueous solution of (1) was incessantly exposed to a UV radiation source and aliquots were taken after reaction times of 1, 2, 3, and 4 h. Analysis by GC/NCI-MS revealed that (1) was continuously degraded under these experimental conditions. However, the total organic carbon (TOC) content remained practically constant during the exposition period, thereby indicating that 1 was not mineralized but continuously converted into other compounds. ESI(+)-MS monitoring revealed that whereas the intensity of the ions of m/z 292/294 ([1 + H](+)) constantly decreased, there was the emergence of other ions of m/z 247/249, 197, 168, and 116 whose intensities simultaneously increased. Their structures were proposed on the basis of: (1) the data of their ESI(+)-MS/MS; (2) their high resolution m/z values; and (3) a plausible reactivity of the thiamethoxam molecule exposed to UV radiation in aqueous solution. Finally, these data allowed us to suggest a reaction route for the photodegradation of 1 in an aqueous medium.
Asunto(s)
Insecticidas/química , Insecticidas/efectos de la radiación , Nitrocompuestos/efectos de la radiación , Oxazinas/efectos de la radiación , Espectrometría de Masa por Ionización de Electrospray/métodos , Tiazoles/efectos de la radiación , Neonicotinoides , Nitrocompuestos/química , Oxazinas/química , Fotoquímica , Fotólisis , Espectrometría de Masas en Tándem/métodos , Tiametoxam , Tiazoles/química , AguaRESUMEN
The potent O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline has been modified by buffer- or acylation-induced imine-to-enamine conversion and then electrophile or radical addition (Xn = D3, F, N3, OH, SMe, COCF3, CF3). Several functionalized GlcNAc-thiazolines show highly selective inhibition of OGA vs human hexosaminidase and thus have promise as tools for targeted investigations of OGA, an enzyme linked to diabetes and neurodegeneration. A new radical addition/fragmentation reaction of the N-(trifluoroacetyl)enamine has been discovered.
Asunto(s)
Inhibidores Enzimáticos/síntesis química , Glucosamina/análogos & derivados , Tiazoles/síntesis química , Cristalografía por Rayos X , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/efectos de la radiación , Radicales Libres/síntesis química , Radicales Libres/farmacología , Radicales Libres/efectos de la radiación , Glucosamina/síntesis química , Glucosamina/farmacología , Glucosamina/efectos de la radiación , Hexosaminidasas/antagonistas & inhibidores , Humanos , Isomerismo , Modelos Moleculares , Conformación Molecular , Relación Estructura-Actividad , Tiazoles/farmacología , Tiazoles/efectos de la radiación , beta-N-Acetilhexosaminidasas/antagonistas & inhibidoresRESUMEN
In an effort to identify new protein kinase inhibitors with increased potency and selectivity, we have developed the microwave-assisted synthesis of thiazolo[5,4-f]quinazolin-9-ones. The effects of eighteen derivatives on CDK1/cyclin B, CDK5/p25, and GSK-3 were investigated. Several turned out to inhibit GSK-3 in the micromolar range. Molecular modeling studies suggest that the most selective GSK-3 inhibitors 7a-d bind into the ATP-binding site through a key hydrogen bond interaction with Val135 and target the specific hydrophobic backpocket of the enzyme.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Quinazolinas/farmacología , Tiazoles/farmacología , Adenosina Trifosfato/química , Sitios de Unión , Cristalografía por Rayos X , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Evaluación Preclínica de Medicamentos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/efectos de la radiación , Enlace de Hidrógeno , Microondas , Modelos Moleculares , Quinazolinas/química , Quinazolinas/efectos de la radiación , Estereoisomerismo , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/efectos de la radiaciónRESUMEN
A microwave-assisted three-component, regioselective one-pot cyclocondensation method has been developed for the synthesis of a series of novel spiro[indole-thiazolidinones] (6a-l) using an environmentally benign procedure at atmospheric pressure in open vessel. This rapid method produces pure products in high yields within few minutes in comparison to a conventional two-step procedure. The crystal structure of one representative compound has been determined by X-ray diffraction. The synthesized compounds have been screened 'in vitro' for antifungal activity against Rhizoctonia solani, Fusarium oxysporum and Collectotrichum capsici. All compounds have shown good activity against these pathogens.
Asunto(s)
Antifúngicos/síntesis química , Bencimidazoles/química , Indoles/síntesis química , Compuestos de Espiro/síntesis química , Triazoles/química , Antifúngicos/química , Antifúngicos/farmacología , Bencimidazoles/efectos de la radiación , Colletotrichum/clasificación , Colletotrichum/efectos de los fármacos , Cristalización , Fusarium/clasificación , Fusarium/efectos de los fármacos , Indoles/química , Indoles/farmacología , Indoles/efectos de la radiación , Microondas , Modelos Moleculares , Estructura Molecular , Rhizoctonia/clasificación , Rhizoctonia/efectos de los fármacos , Compuestos de Espiro/química , Compuestos de Espiro/farmacología , Estereoisomerismo , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/efectos de la radiación , Tiazolidinas , Triazoles/efectos de la radiación , Difracción de Rayos XRESUMEN
An improved simulation model (PCPF-1) has been evaluated for the prediction of the fate of mefenacet in an experimental paddy field. This model simulates the fate and transport of pesticide in paddy water and the top 1 cm of paddy soil. Observed concentrations of mefenacet in the paddy water and the surface soil exponentially decreased from their maximum concentrations of 0.70 mg litre(-1) and 11.3 mg kg(-1), respectively. Predicted mefenacet concentrations both in the water and surface soil were in excellent agreement with those measured during the first 2 weeks after herbicide application, but concentrations in paddy water were appreciably overestimated thereafter. The model simulated mefenacet losses through runoff, percolation and degradation to be respectively 41.9%, 6.4% and 57.3% of applied, and the mass balance error was about -6%. The model simulation implied that drainage and seepage control, especially shortly after application when herbicide concentrations are high, is essential for preventing pesticide losses from paddy fields. In focusing on pesticide concentrations in this early period the PCPF-1 model can be a beneficial tool for risk assessment of pesticide losses and in the evaluation of agricultural management for reducing pesticide pollution associated with paddy rice production.
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Acetanilidas/efectos adversos , Herbicidas/análisis , Modelos Teóricos , Tiazoles/efectos adversos , Acetanilidas/efectos de la radiación , Benzotiazoles , Productos Agrícolas , Herbicidas/efectos de la radiación , Oryza/crecimiento & desarrollo , Residuos de Plaguicidas/análisis , Residuos de Plaguicidas/efectos de la radiación , Transpiración de Plantas , Tiazoles/efectos de la radiación , Contaminantes del Agua/análisis , Contaminantes del Agua/efectos de la radiaciónRESUMEN
High-order multiphoton excitation processes are becoming a reality for fluorescence imaging and phototherapy treatment because they afford minimization of scattered light losses and a reduction of unwanted linear absorption in the living organism transparency window, making them less susceptible to photodamage, while improving the irradiation penetration depth and spatial resolution. We report the four-photon-excited fluorescence emission of (7-benzothiazol-2-yl-9,-didecylfluoren-2-yl)diphenylamine in hexane and its four-photon absorption cross section sigma4' = 8.1 x 10(-109) cm8 s3 photon(-3) for the transition S0 --> S1 when excited at 1600 nm with a tunable optical parametric generator (OPG) pumped by picosecond laser pulses. When pumped at 1200 nm, three-photon absorption was observed, corresponding to the same transition.
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Fluorenos/efectos de la radiación , Transferencia Resonante de Energía de Fluorescencia/métodos , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/efectos de la radiación , Microscopía de Fluorescencia por Excitación Multifotónica/métodos , Tiazoles/efectos de la radiación , Benzotiazoles , Relación Dosis-Respuesta en la Radiación , Rayos LáserRESUMEN
Novel 6-substituted thiazolocarbazole derivatives have been synthesized under microwave irradiation via the corresponding imino-1,2,3-dithiazoles. In vitro antitumor potential of these polyheterocyclic compounds was evaluated. Among all the tested thiazolocarbazoles, compound 10 is the most effective in inhibiting cell growth.
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Antineoplásicos , Carbazoles , Microondas , Tiazoles , Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/efectos de la radiación , Carbazoles/síntesis química , Carbazoles/farmacología , Carbazoles/efectos de la radiación , Línea Celular , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Técnicas In Vitro , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , Tiazoles/síntesis química , Tiazoles/farmacología , Tiazoles/efectos de la radiaciónRESUMEN
In this study, the mitochondrial phototoxicity of the cationic rhodacyanine MKT-077 was investigated by comparing its effects on the inhibition of mitochondrial respiration and the structural integrity of mitochondrial DNA (mtDNA) in the presence and absence of added high-intensity visible light (7.5 J/cm2). Results indicate that photoirradiation significantly enhances the mitochondrial toxicity of MKT-077 at both the biochemical and DNA levels. For example, the concentration of MKT-077 required to achieve one-half maximal inhibition of ADP-stimulated respiration was observed to be 6-fold lower in the presence versus absence of high-intensity light (one-half maximal inhibition at 2.5 versus 15 microg MKT-077/ mg, respectively). In addition, photoirradiation produced a 25-fold increase in inhibition of succinate-cytochrome c reductase activity by MKT-077 (one-half maximal inhibition at 2 versus 50 microg MKT-077/ml, +/-light, respectively) and a 6-fold increase in inhibition of cytochrome oxidase activity (one-half maximal inhibition at 5 versus 30 microg MKT-077/ml, +/-light, respectively). Furthermore, the combination of 25 microg/ml MKT-077 and 7.5 J/cm2 visible light caused significant degradation of mtDNA in isolated rat liver mitochondria, whereas the same concentration of dye in the absence of light had only a modest effect on mtDNA. Evaluation of light-induced MKT-077 lipid peroxidation in mitochondrial membrane fragments by the thiobarbituric acid test and by measurement of nonrespiratory-linked oxygen uptake suggests that mitochondrial phototoxicity by MKT-077 may be the result of lipid peroxidation via reactive oxygen species. These results have important implications with regard to the potential use of MKT-077 in photochemotherapy.
Asunto(s)
Antineoplásicos/farmacología , Mitocondrias/efectos de los fármacos , Consumo de Oxígeno/efectos de los fármacos , Piridinas/farmacología , Tiazoles/farmacología , Animales , Antineoplásicos/efectos de la radiación , Células Cultivadas , ADN Mitocondrial/efectos de los fármacos , Complejo IV de Transporte de Electrones/metabolismo , Haplorrinos , Luz , Peroxidación de Lípido/efectos de los fármacos , Masculino , Mitocondrias/genética , Mitocondrias/fisiología , NADH Deshidrogenasa/metabolismo , Piridinas/efectos de la radiación , Ratas , Ratas Sprague-Dawley , Ácido Succínico/metabolismo , Tiazoles/efectos de la radiaciónRESUMEN
Troglitazone (CS-045) is a new oral antidiabetic drug reported to be effective in insulin-resistant diabetes and to show antihypertensive effects. Photooxidation of troglitazone gave the quinone and quinone epoxide as the major final stable products. An intermediate observed by NMR spectroscopy was shown to be the hydroperoxydienone, which is moderately stable at room temperature. The rate constant of singlet oxygen quenching by troglitazone is 2.14 x 10(8) M(-1) s(-1) and the reaction rate constant in acetone-d6 is 8.64 X 10(6) M(-1) s(-1). Only the chroman ring of troglitazone reacts with and quenches singlet oxygen significantly, and its reactivity and products are analogous to those of alpha-tocopherol. The reactivity of CS-45 toward singlet oxygen is much larger than that of the related compounds lacking the chroman ring.
Asunto(s)
Cromanos/efectos de la radiación , Hipoglucemiantes/efectos de la radiación , Tiazoles/efectos de la radiación , Tiazolidinedionas , Cromanos/química , Estabilidad de Medicamentos , Hipoglucemiantes/química , Cinética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Oxidación-Reducción , Oxígeno , Fotoquímica , Quinonas , Oxígeno Singlete , Relación Estructura-Actividad , Tiazoles/química , TroglitazonaRESUMEN
The photophysics and photochemistry of the 4'-diethylamino derivative of both 2-phenyl-benzothiazole and 2-(2'-hydroxyphenyl)benzothiazole have been studied by nanosecond and microsecond laser flash photolysis and picosecond emission spectroscopy. For the non-hydroxy substituted molecule, the singlet excited state was shown to relax primarily via fluorescence emission, and a very weak triplet transient was observed after laser flash excitation. The 2-(2'-hydroxy-4'-diethylaminophenyl)benzothiazole (AHBT) was shown to undergo excited state intramolecular proton transfer (ESIPT) in the picosecond timescale (k greater than 3 x 10(10) s-1) to form a colored zwitter-ion/keto form in solution at room temperature while the ground state back proton transfer was slower by a factor of approximately 10(5). However, in marked contrast with other derivatives of 2-(2'-hydroxyphenyl)benzothiazole and related molecules, the ESIPT was not the only deactivation process of the lowest singlet excited state of the enol form. Under steady-state excitation at room temperature (and low temperature), the fluorescence emission of the enol form was observed. The T-T absorption of the enol form was also observed and furthermore, the ESIPT was shown to have an activation energy which was estimated to be approximately 4 kJ. None of the foregoing, fluorescence and T-T absorption of the enol nor activation energy for proton transfer have been observed for the parent or derivatives of 2-(2'-hydroxyphenyl)benzothiazoles. The striking new features for the ESIPT photochemistry and photophysics for the 4'-diethylamino derivative of 2-(2'-hydroxyphenyl)benzothiazole are discussed and MO calculations are used to aid in the interpretation of some of the experimental results.