6533b858fe1ef96bd12b595f

RESEARCH PRODUCT

3′-Demethyldihydromaldoxin and dihydromaldoxin, two anti-inflammtory diaryl ethers from a Steganospora species

Dominik H. SchreiberGerhard ErkelMathias JungTill OpatzLouis P. SandjoJohannes C. Liermann

subject

Spectrometry Mass Electrospray IonizationLipopolysaccharideCell SurvivalAntiparasiticmedicine.drug_classAnti-Inflammatory AgentsBiologyTransfectionCell LineInhibitory Concentration 50Lactoneschemistry.chemical_compoundBiosynthesisInterferonDrug DiscoverymedicineProtein biosynthesisAnimalsHumansCXCL10Spiro CompoundsNuclear Magnetic Resonance BiomolecularPharmacologyDose-Response Relationship DrugMolecular StructurePhenyl EthersFungiChemotaxisTransfectionChemokine CXCL10chemistryBiochemistrymedicine.drug

description

CXCL10 (IP-10) is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells such as macrophages and T-lymphocytes and thereby has important roles in chronic inflammatory conditions. In a search for new inhibitors of CXCL10 expression in MonoMac6 (MM6) cells, the new diaryl ether 3'-demethyldihydromaldoxin (1) along with the known compound dihydromaldoxin (2), were isolated from fermentations of a Steganospora species. The structures of the compounds were elucidated by a combination of one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds (1) and (2) inhibited lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced CXCL10 promoter activity in transiently transfected MM6 cells in a dose-dependent manner with IC(50) values of 39-41 μM and also reduced LPS/IFN-γ-induced CXCL10 protein synthesis and excretion.

https://doi.org/10.1038/ja.2012.46