New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity

Suvi Manner, Mikko Vahermo, Malena E. Skogman, Sara Krogerus, Pia M. Vuorela, Jari Yli-Kauhaluoma, Adyary Fallarero, Vânia M. Moreira

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

The combination of the dehydroabietic acid scaffold with different amino acids resulted in the discovery of a new class of hybrid compounds that targets both planktonic and biofilms bacteria in Staphylococcus aureus strains and are far more potent anti-biofilm agents than conventional antibiotics. Unlike dehydroabietic acid, these compounds can disrupt biofilms within a short time period and compromise the integrity of the bacterial membrane. Two of the compounds identified in our study are the most potent abietane-type anti-biofilm agents reported so far and display robust activity against pre-formed biofilms at concentrations only 3-6-fold higher than those required to inhibit biofilm formation. Their easy preparation based on proteolysis-resistant d- and unusual amino acids makes them useful chemical probes to gain a deeper understanding of bacterial biofilms and outstanding candidates for further development into new drugs to fight infections.

LanguageEnglish
Pages68-79
Number of pages12
JournalEuropean Journal of Medicinal Chemistry
Volume102
DOIs
Publication statusPublished - 18 Sep 2015

Fingerprint

Biofilms
Staphylococcus aureus
Bacteria
Derivatives
Membranes
Abietane Diterpenes
Proteolysis
Amino Acids
dehydroabietic acid
Scaffolds
Anti-Bacterial Agents
Infection
Pharmaceutical Preparations

Keywords

  • anti-bacterial agents
  • biofilms
  • cell membrane
  • Diterpenes, Abietane
  • dose-response relationship, drug
  • microbial sensitivity tests
  • plankton
  • Staphylococcus aureus
  • structure-activity relationship

Cite this

Manner, Suvi ; Vahermo, Mikko ; Skogman, Malena E. ; Krogerus, Sara ; Vuorela, Pia M. ; Yli-Kauhaluoma, Jari ; Fallarero, Adyary ; Moreira, Vânia M. / New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity. In: European Journal of Medicinal Chemistry. 2015 ; Vol. 102. pp. 68-79.
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New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity. / Manner, Suvi; Vahermo, Mikko; Skogman, Malena E.; Krogerus, Sara; Vuorela, Pia M.; Yli-Kauhaluoma, Jari; Fallarero, Adyary; Moreira, Vânia M.

In: European Journal of Medicinal Chemistry, Vol. 102, 18.09.2015, p. 68-79.

Research output: Contribution to journalArticle

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T1 - New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity

AU - Manner, Suvi

AU - Vahermo, Mikko

AU - Skogman, Malena E.

AU - Krogerus, Sara

AU - Vuorela, Pia M.

AU - Yli-Kauhaluoma, Jari

AU - Fallarero, Adyary

AU - Moreira, Vânia M.

N1 - Copyright © 2015 Elsevier Masson SAS. All rights reserved.

PY - 2015/9/18

Y1 - 2015/9/18

N2 - The combination of the dehydroabietic acid scaffold with different amino acids resulted in the discovery of a new class of hybrid compounds that targets both planktonic and biofilms bacteria in Staphylococcus aureus strains and are far more potent anti-biofilm agents than conventional antibiotics. Unlike dehydroabietic acid, these compounds can disrupt biofilms within a short time period and compromise the integrity of the bacterial membrane. Two of the compounds identified in our study are the most potent abietane-type anti-biofilm agents reported so far and display robust activity against pre-formed biofilms at concentrations only 3-6-fold higher than those required to inhibit biofilm formation. Their easy preparation based on proteolysis-resistant d- and unusual amino acids makes them useful chemical probes to gain a deeper understanding of bacterial biofilms and outstanding candidates for further development into new drugs to fight infections.

AB - The combination of the dehydroabietic acid scaffold with different amino acids resulted in the discovery of a new class of hybrid compounds that targets both planktonic and biofilms bacteria in Staphylococcus aureus strains and are far more potent anti-biofilm agents than conventional antibiotics. Unlike dehydroabietic acid, these compounds can disrupt biofilms within a short time period and compromise the integrity of the bacterial membrane. Two of the compounds identified in our study are the most potent abietane-type anti-biofilm agents reported so far and display robust activity against pre-formed biofilms at concentrations only 3-6-fold higher than those required to inhibit biofilm formation. Their easy preparation based on proteolysis-resistant d- and unusual amino acids makes them useful chemical probes to gain a deeper understanding of bacterial biofilms and outstanding candidates for further development into new drugs to fight infections.

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KW - biofilms

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