Phaeochromycins A-E, anti-inflammatory polyketides isolated from the soil actinomycete Streptomyces phaeochromogenes LL-P018.
Five new polyketide metabolites, phaeochromycins A-E (1-5), were isolated from an actinomycete designated Streptomyces phaeochromogenes LL-P018, cultured from a soil sample collected from a riverbank in Westevenger, Germany. Phaeochromycins A and C were found to be weak inhibitors of MAPKAP kinase-2 (IC50 = 39 and 130 microM, respectively). The structures of the compounds were determined by spectroscopic analysis, primarily two-dimensional NMR, and revealed that phaeochromycins A, B, C, and E were octaketides, elaborated from a C4 starter unit, related to shunt products of the actinorhodin pathway, namely, mutactin, dehydromutactin, SEK34b, and BSM1. Phaeochromycin D (4) is an unusual partially cyclized degraded octaketide intermediate.
Graziani
Edmund I
EI
Department of Chemical & Screening Sciences, Wyeth Research, 401 N. Middletown Road, Pearl River, New York 10965, USA. graziaei@wyeth.com
Ritacco
Frank V
FV
Bernan
Valerie S
VS
Telliez
Jean-Baptiste
JB
D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D005858:Germany; D006801:Humans; D020128:Inhibitory Concentration 50; D047908:Intracellular Signaling Peptides and Proteins; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011753:Pyrones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D012988:Soil Microbiology; D013302:Streptomyces / Q000737:chemistry*; D000099190:MAP-Kinase-Activated Kinase 2
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011753:Pyrones; D000099190:MAP-Kinase-Activated Kinase 2; C504637:mutactin; C483526:wailupemycin B