RESUMEN
A series of oxazolidinone and indole derivatives were synthesized and evaluated as IL-6 signaling blockers by measuring the effects of these compounds on IL-6-induced luciferase expression in human hepatocarcinoma HepG2 cells transfected with p-STAT3-Luc. Among different compounds screened, compound 4d was emerged as the most potent IL-6 signaling blockers with IC50 value of 5.9 µM which was much better than (+)-Madindoline A (IC50=21 µM), a known inhibitor of IL-6.
Asunto(s)
Interleucina-6/metabolismo , Oxazolidinonas/química , Transducción de Señal/efectos de los fármacos , Sitios de Unión , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Cristalografía por Rayos X , Células Hep G2 , Humanos , Indoles/química , Concentración 50 Inhibidora , Interleucina-6/antagonistas & inhibidores , Simulación del Acoplamiento Molecular , Oxazolidinonas/síntesis química , Oxazolidinonas/farmacología , Estructura Terciaria de Proteína , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Relación Estructura-ActividadRESUMEN
A variety of diazepinone derivatives were prepared from α-amino acids and amino alcohols by a new synthetic methodology based on ring closing metathesis as a key step. The diazepinones were coupled with ribose derivatives to afford novel diazepinone nucleosides. Among them, (4R)-1-ribosyl-4-methyl-3,4-dihydro-1H-1,3-diazepin-2(7H)-one (3) showed a potent inhibitory effect (K(i) = 145.97 ± 4.87 nM) against human cytidine deaminase.
Asunto(s)
Azepinas/síntesis química , Azepinas/farmacología , Citidina Desaminasa/antagonistas & inhibidores , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/farmacología , Azepinas/química , Técnicas de Química Sintética , Inhibidores Enzimáticos/química , HumanosRESUMEN
The first total synthesis of the naturally occurring benzofurans, moracins O and P was achieved using a Sonogashira cross coupling reaction followed by in situ cyclization, and the absolute configuration of natural moracin O was established.