Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain.

2.50
Hdl Handle:
http://hdl.handle.net/10033/24112
Title:
Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain.
Authors:
Surup, Frank; Shojaei, Heydar; von Zezschwitz, Paultheo; Kunze, Brigitte; Grond, Stephanie
Abstract:
Two 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.
Affiliation:
Institute of Organic and Biomolecular Chemistry, Georg-August-Universität Göttingen, Tammannstrasse 2, 37077 Göttingen, Germany.
Citation:
Iromycins from Streptomyces sp. and from synthesis: new inhibitors of the mitochondrial electron transport chain. 2008, 16 (4):1738-46 Bioorg. Med. Chem.
Journal:
Bioorganic & medicinal chemistry
Issue Date:
15-Feb-2008
URI:
http://hdl.handle.net/10033/24112
DOI:
10.1016/j.bmc.2007.11.023
PubMed ID:
18054490
Type:
Article
Language:
en
ISSN:
1464-3391
Appears in Collections:
collections of the research group microbial communication (KOM)

Full metadata record

DC FieldValue Language
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.en
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

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