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

A1 Originalartikel i en vetenskaplig tidskrift (referentgranskad)


Interna författare/redaktörer


Publikationens författare: Suvi Manner, Mikko Vahermo, Malena E. Skogman, Sara Krogerus, Pia M. Vuorela, Jari Yli-Kauhaluoma, Adyary Fallarero, Vânia M. Moreira
Förläggare: Elsevier Masson
Publiceringsår: 2015
Tidskrift: European Journal of Medicinal Chemistry
Volym: 102
Artikelns första sida, sidnummer: 68
Artikelns sista sida, sidnummer: 79
eISSN: 1768-3254


Abstrakt

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 3e6-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.
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.


Nyckelord

Amino acids, Antimicrobial, Biofilms, Dehydroabietic acid, Diterpenoids, Natural products

Senast uppdaterad 2019-14-11 vid 05:29