RESUMEN
A new fluorescent biarsenical peptide labeling probe was synthesized and labeled with the radioactive isotopes 11C and 18F. The utility of this probe was demonstrated by installing each of these isotopes into a melanocortin 1 receptor (MC1R) binding peptide, which targets melanoma tumors. Its applicability was further showcased by subsequent in vitro imaging in cells as well as in vivo imaging in melanoma xenograft mice by fluorescence and positron emission tomography.
Asunto(s)
Arsenicales/química , Colorantes Fluorescentes/química , Melanoma Experimental/diagnóstico por imagen , Tomografía de Emisión de Positrones , Animales , Línea Celular Tumoral , Xenoinjertos , Melanoma Experimental/metabolismo , Ratones , Péptidos/metabolismo , Receptor de Melanocortina Tipo 1/metabolismoRESUMEN
A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on Abeta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer Abeta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric Abeta-peptide.
Asunto(s)
Péptidos beta-Amiloides/química , Ácidos Carboxílicos/química , Microondas , Péptidos/antagonistas & inhibidores , Piridonas/química , Espectroscopía de Resonancia Magnética , Microscopía de Fuerza Atómica , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría InfrarrojaRESUMEN
By employing microwave-assisted organic synthesis (MAOS) efficient conditions to introduce aminomethylene substituents in highly substituted bicyclic 2-pyridones have been established. Primary amino methylene substituents were introduced via a cyanodehalogenation followed by a borane dimethyl sulfide reduction of the afforded nitrile. In both of these transformations, microwave irradiation proved to be superior to traditional conditions and the primary amines were obtained in good overall yields (55-58% over three steps). To incorporate tertiary aminomethylene substituents in the 2-pyridone framework, a microwave-assisted Mannich reaction using preformed iminium salts proved to be effective. Thus highly substituted 2-pyridones were obtained in 48-93% yields.