uu.seUppsala University Publications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Development and evaluation of cationic amphiphilic antimicrobial 2,5-diketopiperazines
Univ Aberdeen, Dept Chem, Marine Biodiscovery Ctr, Old Aberdeen AB24 3UE, Scotland;UiT Arctic Univ Norway, Dept Chem, Tromso, Norway.
Univ Gothenburg, Sahlgrenska Acad, Dept Infect Dis, Gothenburg, Sweden.
RISE Res Inst Sweden, Dept Chem & Mat, Boras, Sweden.
UiT Arctic Univ Norway, Dept Chem, Tromso, Norway.
Show others and affiliations
2018 (English)In: Journal of Peptide Science, ISSN 1075-2617, E-ISSN 1099-1387, Vol. 24, no 7, article id e3090Article in journal (Refereed) Published
Abstract [en]

Both pathogenic bacteria and fungi are developing resistance to common antimicrobial treatment at an alarming rate. To counteract this development, it is of essence to develop new classes of antimicrobial agents. One such class is antimicrobial peptides, most of which are derived from the innate immune system. In this study, a series of novel 2,5-diketopiperazines were designed, synthesized, and evaluated for their antimicrobial abilities. The compounds were designed to probe the pharmacophore dictated for short linear mimics of antimicrobial cationic peptides, and as such, the compounds contain a range of cationic and hydrophobic functionalities. Several of the prepared compounds displayed high antimicrobial activities toward bacteria and also against human pathogenic fungi. Of particular interest was the high activity toward fungal strains with an inherent increased resistance toward conventional antifungal agents. The most effective compounds displayed inhibition of Candida glabrata and Candida krusei growth at concentrations between 4 and 8 mu g/mL, which is comparable to commercial antifungal agents in use. Structure activity relationship studies revealed a similar dependence on cationic charge and the volume of the hydrophobic bulk as for linear cationic antimicrobial peptides. Finally, the hemolytic activity of selected compounds was evaluated, which revealed a potential to produce active compounds with attenuation of unwanted hemolysis. The findings highlight the potential of cyclic cationic amphiphilic peptidomimetics as a class of promising compounds for the treatment of infections caused by microorganisms with an increased resistance to conventional antimicrobial agents.

Place, publisher, year, edition, pages
WILEY , 2018. Vol. 24, no 7, article id e3090
Keywords [en]
2, 5-diketopiperazine, antifungal agents, antimicrobial, Candida krusei, MRSA, structure-activity relationship
National Category
Organic Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-362848DOI: 10.1002/psc.3090ISI: 000440144700005PubMedID: 29845683OAI: oai:DiVA.org:uu-362848DiVA, id: diva2:1255750
Conference
7th International Meeting on Antimicrobial Peptides, AUG 25-27, 2017, Univ Copenhagen, Copenhagen, DENMARK
Funder
VINNOVA, 2014-01435The Research Council of Norway, ES508288Available from: 2018-10-15 Created: 2018-10-15 Last updated: 2019-12-14Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Authority records BETA

Nilsson Ekdahl, Kristina

Search in DiVA

By author/editor
Nilsson Ekdahl, Kristina
By organisation
Department of Immunology, Genetics and Pathology
In the same journal
Journal of Peptide Science
Organic Chemistry

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 47 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf