The irpexans, a new group of biologically active metabolites produced by the basidiomycete Irpex sp. 93028.
Five novel antibiotics described as irpexans (1, 2, 3a, 3b, 4) were isolated from fermentations of an Irpex species in the course of a screening for new inhibitors of AP-1 and NF-kappaB mediated signal transduction pathways in COS-7 cells using secreted alkaline phosphatase (SEAP) as a reporter gene. The expression of an AP-1 and NF-kappaB driven SEAP reporter gene was inhibited in a dose dependent manner with 14-acetoxy-15-hydroxyirpexan (3b) being the most potent compound, followed by 14,15-irpexanoxide (2), 14,15-dihydroxyirpexan (3a) and 14-acetoxy-22,23-dihydro-15,23-dihydroxyirpexan (4). Irpexan (1) exhibited no activity. The irpexans (1, 2, 3a, 3b, 4) are characterized by weak cytotoxic but neither antibacterial nor antifungal activities. All five compounds are terpenoids with a mannose moiety. The structures were elucidated by spectroscopic methods.
Silberborth
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S
LB Biotechnologie der Universität, Kaiserslautern, Germany.
Erkel
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G
Anke
T
T
Sterner
O
O
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001487:Basidiomycota / Q000145:classification / Q000254:growth & development / Q000378:metabolism*; D019556:COS Cells; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005233:Fatty Alcohols / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D017930:Genes, Reporter; D009682:Magnetic Resonance Spectroscopy; D008362:Mannosides / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000900:Anti-Bacterial Agents; D005233:Fatty Alcohols; D008362:Mannosides; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D000469:Alkaline Phosphatase