Melithiazols, new beta-methoxyacrylate inhibitors of the respiratory chain isolated from myxobacteria. Production, isolation, physico-chemical and biological properties.
New antibiotic compounds, melithiazols, were isolated from the culture broth of strains of the myxobacteria Melittangium lichenicola, Archangium gephyra, and Myxococcus stipitatus. The compounds belong to the group of beta-methoxyacrylate (MOA) inhibitors and are related to the myxothiazols. The melithiazols show high antifungal activity, but are less toxic than myxothiazol A and its methyl ester in a growth inhibition assay with mouse cell cultures. The melithiazols inhibit NADH oxidation by submitochondrial particles from beef heart. Melithiazol A blocks the electron transport within the bc1-segment (complex III) and causes a red shift in the reduced spectrum of cytochrome b.
Sasse
F
F
GBF, Gesellschaft für Biotechnologische Forschung mbH, Abteilung Naturstoffbiologie, Braunschweig, Germany.
Böhlendorf
B
B
Herrmann
M
M
Kunze
B
B
Forche
E
E
Steinmetz
H
H
Höfle
G
G
Reichenbach
H
H
Hermann
M
M
D000179:Acrylates / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*; D019069:Cell Respiration / Q000187:drug effects*; D003573:Cytochrome b Group / Q000187:drug effects / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004734:Energy Metabolism / Q000187:drug effects; D005231:Fatty Acids, Unsaturated / Q000737:chemistry / Q000494:pharmacology; D005285:Fermentation; D006801:Humans; D007223:Infant; D020128:Inhibitory Concentration 50; D008689:Methacrylates; D051379:Mice; D008826:Microbial Sensitivity Tests; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D009231:Myxococcales / Q000737:chemistry / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D000073739:Strobilurins; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology*
D000179:Acrylates; D000935:Antifungal Agents; D003573:Cytochrome b Group; D005231:Fatty Acids, Unsaturated; D008689:Methacrylates; D000073739:Strobilurins; D013844:Thiazoles; C401242:melithiazol A; C401243:melithiazol B; C401244:melithiazol C; D009243:NAD; C008556:mucidin; C030517:myxothiazol; C023324:oudemansin