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Mar Drugs. 2014 Jan 28;12(2):799-821. doi: 10.3390/md12020799.

Isolation and characterization of anti-adenoviral secondary metabolites from marine actinobacteria.

Author information

  • 1Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden. marten.strand@climi.umu.se.
  • 2Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden. marcus.carlsson@chem.umu.se.
  • 3Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden. hanna.uvell@chem.umu.se.
  • 4Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden. koushikul.islam@climi.umu.se.
  • 5Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden. karin.edlund@climi.umu.se.
  • 6Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden. inger.cullman@chem.umu.se.
  • 7Department of Chemistry, Faculty of Science and Technology, University of Tromsø, Tromsø 9037, Norway. bjorn.altermark@uit.no.
  • 8Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden. mei.ya-fang@climi.umu.se.
  • 9Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden. mikael.elofsson@chem.umu.se.
  • 10Department of Chemistry, Faculty of Science and Technology, University of Tromsø, Tromsø 9037, Norway. nils-peder.willassen@uit.no.
  • 11Division of Virology, Department of Clinical Microbiology, Umeå University, Umeå SE-90185, Sweden. goran.wadell@climi.umu.se.
  • 12Laboratories for Chemical Biology, Department of Chemistry, Umeå University, Umeå SE-90187, Sweden. fredrik.almqvist@chem.umu.se.

Abstract

Adenovirus infections in immunocompromised patients are associated with high mortality rates. Currently, there are no effective anti-adenoviral therapies available. It is well known that actinobacteria can produce secondary metabolites that are attractive in drug discovery due to their structural diversity and their evolved interaction with biomolecules. Here, we have established an extract library derived from actinobacteria isolated from Vestfjorden, Norway, and performed a screening campaign to discover anti-adenoviral compounds. One extract with anti-adenoviral activity was found to contain a diastereomeric 1:1 mixture of the butenolide secondary alcohols 1a and 1b. By further cultivation and analysis, we could isolate 1a and 1b in different diastereomeric ratio. In addition, three more anti-adenoviral butenolides 2, 3 and 4 with differences in their side-chains were isolated. In this study, the anti-adenoviral activity of these compounds was characterized and substantial differences in the cytotoxic potential between the butenolide analogs were observed. The most potent butenolide analog 3 displayed an EC50 value of 91 μM and no prominent cytotoxicity at 2 mM. Furthermore, we propose a biosynthetic pathway for these compounds based on their relative time of appearance and structure.

PMID:
24477283
PMCID:
PMC3944516
DOI:
10.3390/md12020799
[PubMed - indexed for MEDLINE]
Free PMC Article
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