3'-Demethyldihydromaldoxin and dihydromaldoxin, two anti-inflammtory diaryl ethers from a Steganospora species.
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.
Department of Molecular Biotechnology and Systems Biology, University of Kaiserslautern, Kaiserslautern, Germany.
Dominik
D
Schreiber
Mathias
M
Jung
Louis P
LP
Sandjo
Johannes C
JC
Liermann
Till
T
Opatz
Gerhard
G
Erkel
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D054357:Chemokine CXCL10 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010647:Phenyl Ethers / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D021241:Spectrometry, Mass, Electrospray Ionization; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014162:Transfection
D000893:Anti-Inflammatory Agents; D054357:Chemokine CXCL10; D007783:Lactones; D010647:Phenyl Ethers; D013141:Spiro Compounds; C562279:maldoxin