title: New derivatives of dehydroabietic acid target planktonic and biofilm bacteria in Staphylococcus aureus and effectively disrupt bacterial membrane integrity.
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.
authors.affiliation: Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Abo Akademi University, BioCity, Artillerigatan 6 A, FI-20520 Turku, Finland.
authors.forename: Suvi
authors.initials: S
authors.lastname: Manner
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
authors.forename: Mikko
authors.initials: M
authors.lastname: Vahermo
authors.affiliation: Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
authors.forename: Malena E
authors.initials: ME
authors.lastname: Skogman
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
authors.forename: Sara
authors.initials: S
authors.lastname: Krogerus
authors.affiliation: Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
authors.forename: Pia M
authors.initials: PM
authors.lastname: Vuorela
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland.
authors.forename: Jari
authors.initials: J
authors.lastname: Yli-Kauhaluoma
authors.affiliation: Pharmaceutical Biology, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland. Electronic address: adyary.fallarero@helsinki.fi.
authors.forename: Adyary
authors.initials: A
authors.lastname: Fallarero
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Viikinkaari 5 E, FI-00014 Helsinki, Finland. Electronic address: vania.moreira@helsinki.fi.
authors.forename: Vânia M
authors.initials: VM
authors.lastname: Moreira
mesh_terms: D045784:Abietanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008826:Microbial Sensitivity Tests; D010933:Plankton / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D045784:Abietanes; D000900:Anti-Bacterial Agents; C013913:dehydroabietic acid
keywords: Amino acids; Antimicrobial; Biofilms; Dehydroabietic acid; Diterpenoids; Natural products