Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues.

2.50
Hdl Handle:
http://hdl.handle.net/10033/304702
Title:
Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues.
Authors:
Li, Xu-Wen; Herrmann, Jennifer; Zang, Yi; Grellier, Philippe; Prado, Soizic; Müller, Rolf; Nay, Bastien
Abstract:
Aurachins are myxobacterial 3-farnesyl-4(1H)-quinolone derived compounds initially described as respiratory chain inhibitors, more specifically as inhibitors of various cytochrome complexes. They are also known as potent antibiotic compounds. We describe herein the first synthesis of aurachin D through a key Conrad-Limpach reaction. The same strategy was used to reach some ring as opposed to chain analogues, allowing for the description of structure-activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was found on Plasmodium falciparum with a selectivity index of 345, compared to Vero cells, for the natural product and its geranyl analogue. The loss of mitochondrial membrane potential induced by aurachins in human U-2 OS osteosarcoma cells was studied, showing the best activity for aurachin D and a naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic cyclization.
Affiliation:
Muséum National d'Histoire Naturelle, Unité Molécules de Communication et Adaptation des Micro-organismes (UMR 7245 CNRS-MNHN), 57 rue Cuvier (CP 54), 75005 Paris, France.
Citation:
Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues. 2013, 9:1551-8 Beilstein J Org Chem
Publisher:
Beilstein-Institut Zur Forderung der Chemischen Wissenschaften
Journal:
Beilstein journal of organic chemistry
Issue Date:
2013
URI:
http://hdl.handle.net/10033/304702
DOI:
10.3762/bjoc.9.176
PubMed ID:
23946854
Type:
Article
Language:
en
ISSN:
1860-5397
Appears in Collections:
publications of the department of microbial natural substances ([HIPS]MINS)

Full metadata record

DC FieldValue Language
dc.contributor.authorLi, Xu-Wenen
dc.contributor.authorHerrmann, Jenniferen
dc.contributor.authorZang, Yien
dc.contributor.authorGrellier, Philippeen
dc.contributor.authorPrado, Soizicen
dc.contributor.authorMüller, Rolfen
dc.contributor.authorNay, Bastienen
dc.date.accessioned2013-10-29T13:44:51Z-
dc.date.available2013-10-29T13:44:51Z-
dc.date.issued2013-
dc.identifier.citationSynthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues. 2013, 9:1551-8 Beilstein J Org Chemen
dc.identifier.issn1860-5397-
dc.identifier.pmid23946854-
dc.identifier.doi10.3762/bjoc.9.176-
dc.identifier.urihttp://hdl.handle.net/10033/304702-
dc.description.abstractAurachins are myxobacterial 3-farnesyl-4(1H)-quinolone derived compounds initially described as respiratory chain inhibitors, more specifically as inhibitors of various cytochrome complexes. They are also known as potent antibiotic compounds. We describe herein the first synthesis of aurachin D through a key Conrad-Limpach reaction. The same strategy was used to reach some ring as opposed to chain analogues, allowing for the description of structure-activity relationships. Biological screening of the analogues showed antiparasitic, cytotoxic, antibacterial and antifungal activities, and depletion of the mitochondrial membrane potential. The strongest activity was found on Plasmodium falciparum with a selectivity index of 345, compared to Vero cells, for the natural product and its geranyl analogue. The loss of mitochondrial membrane potential induced by aurachins in human U-2 OS osteosarcoma cells was studied, showing the best activity for aurachin D and a naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic cyclization.en
dc.language.isoenen
dc.publisherBeilstein-Institut Zur Forderung der Chemischen Wissenschaftenen
dc.rightsArchived with thanks to Beilstein journal of organic chemistryen
dc.titleSynthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues.en
dc.typeArticleen
dc.contributor.departmentMuséum National d'Histoire Naturelle, Unité Molécules de Communication et Adaptation des Micro-organismes (UMR 7245 CNRS-MNHN), 57 rue Cuvier (CP 54), 75005 Paris, France.en
dc.identifier.journalBeilstein journal of organic chemistryen

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