ABSTRACT
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.
Subject(s)
Interleukin-6/metabolism , Oxazolidinones/chemistry , Signal Transduction/drug effects , Binding Sites , Bridged Bicyclo Compounds, Heterocyclic/chemistry , Crystallography, X-Ray , Hep G2 Cells , Humans , Indoles/chemistry , Inhibitory Concentration 50 , Interleukin-6/antagonists & inhibitors , Molecular Docking Simulation , Oxazolidinones/chemical synthesis , Oxazolidinones/pharmacology , Protein Structure, Tertiary , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Structure-Activity RelationshipABSTRACT
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.
Subject(s)
Azepines/chemical synthesis , Azepines/pharmacology , Cytidine Deaminase/antagonists & inhibitors , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/pharmacology , Azepines/chemistry , Chemistry Techniques, Synthetic , Enzyme Inhibitors/chemistry , HumansABSTRACT
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.
