RESUMEN
'Bended' 1, 3 or 'linear' 2 pyrrolidino-fused (aza)carbazoles were prepared and screened towards a few cancer-related targets. Whereas 'bended' derivatives 1 and 3 proved to be weakly toxic, several members of the 'linear' family strongly interact with DNA, especially derivative 28a.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Carbazoles/química , Carbazoles/farmacología , Carbolinas/química , Carbolinas/farmacología , Pirroles/química , Animales , Antineoplásicos/química , Antineoplásicos/toxicidad , Proteína Quinasa CDC2/antagonistas & inhibidores , Proteína Quinasa CDC2/metabolismo , Carbazoles/síntesis química , Carbazoles/toxicidad , Carbolinas/síntesis química , Carbolinas/toxicidad , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , ADN/genética , ADN/metabolismo , Huella de ADN , ADN-Topoisomerasas de Tipo I/metabolismo , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/toxicidad , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Glucógeno Sintasa Quinasa 3 beta , Indoles/química , Concentración 50 Inhibidora , Ratones , Estructura Molecular , Desnaturalización de Ácido Nucleico , Relación Estructura-Actividad , Temperatura , Volumetría , Inhibidores de Topoisomerasa IRESUMEN
Direct high-performance liquid chromatographic chiral separation of numerous underivatized unnatural amino acids on a ristocetin A-bonded chiral stationary phase used in the reversed-phase and in the polar organic chromatographic modes is reported. The effects of different parameters such as mobile phase composition, temperature, and the structure of the analytes on the selectivity in both chromatographic modes are discussed. By variation of the parameters, the separation of the stereoisomers was optimized and, as a result, baseline resolution was achieved in most cases.
Asunto(s)
Aminoácidos/química , Aminoácidos/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Estructura Molecular , Ristocetina , Estereoisomerismo , TemperaturaRESUMEN
Five-step synthetic routes of two new polyfused heterocycles: indazolo[3,2-a]-beta-carboline (3) and benzo[4',5'][1,2,3]triazino[6,1-a]-beta-carbolinium salt (10) applying Pd(0)-catalyzed cross-coupling reaction have been elaborated.
Asunto(s)
Carbolinas/química , Compuestos Heterocíclicos/química , Sustancias Intercalantes/químicaRESUMEN
We describe selective CCKA receptor antagonists, based on the 1-oxo-1,2,3,4-tetrahydro-beta-carboline-3-carboxylic acid core. Selectivity A vs B is discussed on the basis of molecular modelling. Chemical preparation uses electrophilic cyclization of isocyanates derivating from unnatural tryptophan esters. A stereoselective version of the reaction is given. A few peptides incorporating unnatural tryptophans are prepared, with a view of SAR.