RESUMO
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.
Assuntos
Interleucina-6/metabolismo , Oxazolidinonas/química , Transdução de Sinais/efeitos dos fármacos , Sítios de Ligação , Compostos Bicíclicos Heterocíclicos com Pontes/química , Cristalografia por Raios X , Células Hep G2 , Humanos , Indóis/química , Concentração Inibidora 50 , Interleucina-6/antagonistas & inibidores , Simulação de Acoplamento Molecular , Oxazolidinonas/síntese química , Oxazolidinonas/farmacologia , Estrutura Terciária de Proteína , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Relação Estrutura-AtividadeRESUMO
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.
Assuntos
Azepinas/síntese química , Azepinas/farmacologia , Citidina Desaminase/antagonistas & inibidores , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Azepinas/química , Técnicas de Química Sintética , Inibidores Enzimáticos/química , HumanosRESUMO
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.
