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dc.contributor.authorSurup, Frank
dc.contributor.authorShojaei, Heydar
dc.contributor.authorvon Zezschwitz, Paultheo
dc.contributor.authorKunze, Brigitte
dc.contributor.authorGrond, Stephanie
dc.date.accessioned2008-04-24T08:27:21Z
dc.date.available2008-04-24T08:27:21Z
dc.date.issued2008-02-15
dc.identifier.citationIromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain. 2008, 16 (4):1738-46 Bioorg. Med. Chem.en
dc.identifier.issn1464-3391
dc.identifier.pmid18054490
dc.identifier.doi10.1016/j.bmc.2007.11.023
dc.identifier.urihttp://hdl.handle.net/10033/24112
dc.description.abstractTwo new alpha-pyridone metabolites, iromycins E and F, were isolated from cultures of strain Streptomyces sp. Dra 17, thus expanding the recently discovered iromycin family. The inhibitory potential on the mitochondrial respiratory chain was examined and revealed that iromycin metabolites block NADH oxidation in beef heart submitochondrial particles with different efficacy, yet remarkably show only very low cytotoxicity. Difference spectroscopic studies indicated that iromycins inhibit the electron transport at the site of complex I (NADH-ubiquinone oxidoreductase). Derivatives of the natural products were semisynthetically prepared and provided detailed insights into structure-activity relationships. Drawn from these results, there are strong similarities with the piericidins, which are among the most potent complex I inhibitors of the mitochondrial electron transport chain. Furthermore, total synthesis afforded new analogues, and the non-natural iromycin S (IC50 = 58 ng/mL) emerged as the most active compound, thus opening avenues of future studies with the iromycins as new valuable biochemical tools.
dc.language.isoenen
dc.titleIromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain.en
dc.typeArticleen
dc.contributor.departmentInstitute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.en
dc.identifier.journalBioorganic & medicinal chemistryen
refterms.dateFOA2018-06-13T00:38:23Z
html.description.abstractTwo new alpha-pyridone metabolites, iromycins E and F, were isolated from cultures of strain Streptomyces sp. Dra 17, thus expanding the recently discovered iromycin family. The inhibitory potential on the mitochondrial respiratory chain was examined and revealed that iromycin metabolites block NADH oxidation in beef heart submitochondrial particles with different efficacy, yet remarkably show only very low cytotoxicity. Difference spectroscopic studies indicated that iromycins inhibit the electron transport at the site of complex I (NADH-ubiquinone oxidoreductase). Derivatives of the natural products were semisynthetically prepared and provided detailed insights into structure-activity relationships. Drawn from these results, there are strong similarities with the piericidins, which are among the most potent complex I inhibitors of the mitochondrial electron transport chain. Furthermore, total synthesis afforded new analogues, and the non-natural iromycin S (IC50 = 58 ng/mL) emerged as the most active compound, thus opening avenues of future studies with the iromycins as new valuable biochemical tools.


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