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

Abstract

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 0 -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)

SF002-96-1, a new drimane sesquiterpene lactone from an Aspergillus species, inhibits survivin expression

“…The mRNA expression in human Colo 320 cells was analyzed by two-step real-time RT-PCR as described before [39] with gene-specific primers for human survivin (Genbank Accession NM001168) forward: 5´-ACCAGGTGAGAAGTGAGGGA-3´ and reverse: 5´-AACAGTAGAGGAGCCAGGGA-3´ (size of the PCR product is 309 bp) and GAPDH (Genbank Accession M33197) forward: 5’-CCTCCGGGAAACTGTGG-3’ and reverse: 5’-AGTGGGGACACGGAAG-3’ (size of the PCR product is 140 bp). Relative mRNA amounts were determined using the mathematical model for relative quantification in real-time PCR proposed by Pfaffl [40].…”

Naturally Occurring Asterric Acid Analogs: Chemistry and Biology

“…Its structure was established by detailed analysis of its NMR data, and the position of the chlorine atom in penicillither ( 28) was postulated at C-6 based on the possible biosynthetic pathway from the co-isolated chlorobenzopheneone. 31 Chemical investigation into a fungus Aspergillus iizukae isolated from coastal saline soil in Kenli, China, led to purify a new analog iizukine A (29) along with several known ones, and the chlorine atom was connected at C-4 not C-6 in iizukine A (29), different from penicillither (28), though similar NMR data were observed in these metabolites. 32 Diphenyl ether derivatives are kind of common fungi secondary metabolites.…”

“…In a search for new inhibitors of CXCL10 expression, a new diaryl ether 3′-demethyldihydromaldoxin ( 26 ) along with the known analog dihydromaldoxin ( 14 ), was isolated from Steganospora sp. IBWFE07110 . The structures were analyzed by a combination of 1D-, 2D-NMR, and MS spectroscopies together with comparison of asterric acid NMR data.…”

“…The mechanism of anti-inflammation was further clarified to be relevant to the suppression effects performed by asterric acid analogs on ROS, reactive nitrogen species (RNS), and pro-inflammation mediators. CXCL10 is a highly inducible chemoattractant, which contributes to the recruitment of inflammatory cells such as macrophages and T-lymphocytes, thereby playing an important role in chronic inflammatory conditions. , In 2012, Erkel et al found dihydromaldoxin ( 14 ) and 3′-demethyldihydromaldoxin ( 26 ) inhibited lipopolysaccharide (LPS)/interferon-γ (IFN-γ)-induced CXCL10 promoter activity in transiently transfected MM6 cells, with the reduction of LPS/IFN-γ-induced CXCL10 protein synthesis and excretion …”

“…To date, there are more than 50 asterric acid analogs isolated from diverse bioresources mainly from fungi, including Aspergillus, Oospora, Penicillium, Chrysosporium, Pestalotiopsis, Scytalidium, Leptosphaerulina, Xylaria, Neoplaconema, Geomyces, Corynespora, Steganospora, Phoma, Verticillium, Alternaria, Pleosporales, Pseudogymnoascus, Saccharomonospora (Table ). − In addition, several reports claimed that some analogs were ever isolated from different plants, − ,, which suggested an interesting question whether asterric acid analogs isolated from plants might be biosynthesized through the plant endophytic fungi or pathogens.…”