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dc.contributor.authorLanger, Manuel K
dc.contributor.authorRahman, Ataur
dc.contributor.authorDey, Hymonti
dc.contributor.authorAnderssen, Trude
dc.contributor.authorBlencke, Hans-Matti
dc.contributor.authorHaug, Tor
dc.contributor.authorStensvåg, Klara
dc.contributor.authorStrøm, Morten B.
dc.contributor.authorBayer, Annette
dc.date.accessioned2023-08-31T10:52:20Z
dc.date.available2023-08-31T10:52:20Z
dc.date.issued2023-01-24
dc.description.abstractMimics of antimicrobial peptides (AMPs) have been proposed as a promising class of antimicrobial agents. We report the analysis of five tetrasubstituted, cationic, amphipathic heterocycles as potential AMP mimics. The analysis showed that the heterocyclic scaffold had a strong influence on the haemolytic activity of the compounds, and the hydantoin scaffold was identified as a promising template for drug lead development. Subsequently, a total of 20 hydantoin derivatives were studied for their antimicrobial potency and haemolytic activity. We found 19 of these derivatives to have very low haemolytic toxicity and identified three lead structures, <b>2dA</b>, <b>6cG</b>, and <b>6dG</b> with very promising broad-spectrum antimicrobial activity. Lead structure <b>6dG</b> displayed minimum inhibitory concentration (MIC) values as low as 1 μg/mL against Gram-positive bacteria and 4–16 μg/mL against Gram-negative bacteria. Initial mode of action (MoA) studies performed on the amine derivative <b>6cG</b>, utilizing a luciferase-based biosensor assay, suggested a strong membrane disrupting effect on the outer and inner membrane of Escherichia coli. Our findings show that the physical properties and structural arrangement induced by the heterocyclic scaffolds are important factors in the design of AMP mimics.en_US
dc.identifier.citationLanger MK, Rahman A, Dey H, Anderssen T, Blencke H, Haug T, Stensvåg K, Strøm mbs, Bayer A. Investigation of tetrasubstituted heterocycles reveals hydantoins as a promising scaffold for development of novel antimicrobials with membranolytic properties. European Journal of Medicinal Chemistry. 2023;249
dc.identifier.cristinIDFRIDAID 2112539
dc.identifier.doi10.1016/j.ejmech.2023.115147
dc.identifier.issn0223-5234
dc.identifier.issn1768-3254
dc.identifier.urihttps://hdl.handle.net/10037/30591
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.relation.ispartofRahman, A. (2024). Bioactivity profiling and mode of action studies of antibacterial and antibiofilm agents of marine origin. (Doctoral thesis). <a href=https://hdl.handle.net/10037/32414>https://hdl.handle.net/10037/32414</a>.
dc.relation.journalEuropean Journal of Medicinal Chemistry
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.rightsAttribution 4.0 International (CC BY 4.0)en_US
dc.titleInvestigation of tetrasubstituted heterocycles reveals hydantoins as a promising scaffold for development of novel antimicrobials with membranolytic propertiesen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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Attribution 4.0 International (CC BY 4.0)
Med mindre det står noe annet, er denne innførselens lisens beskrevet som Attribution 4.0 International (CC BY 4.0)