1.00
HDL Handle:
http://hdl.handle.net/10033/243651
Title:
Antimicrobial and biofilm inhibiting diketopiperazines.
Authors:
de Carvalho, M P; Abraham, W-R
Abstract:
Diketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.
Affiliation:
Helmholtz Center for Infection Research, Chemical Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany. wolf-rainer.abraham@helmholtz-hzi.de.
Citation:
Antimicrobial and biofilm inhibiting diketopiperazines. 2012, 19 (21):3564-77 Curr. Med. Chem.
Journal:
Current medicinal chemistry
Issue Date:
1-Jul-2012
URI:
http://hdl.handle.net/10033/243651
PubMed ID:
22709011
Type:
Article
Language:
en
ISSN:
1875-533X
Appears in Collections:
Publications of RG Chemical Microbiology (CMIK)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorde Carvalho, M Pen_GB
dc.contributor.authorAbraham, W-Ren_GB
dc.date.accessioned2012-09-12T14:42:20Z-
dc.date.available2012-09-12T14:42:20Z-
dc.date.issued2012-07-01-
dc.identifier.citationAntimicrobial and biofilm inhibiting diketopiperazines. 2012, 19 (21):3564-77 Curr. Med. Chem.en_GB
dc.identifier.issn1875-533X-
dc.identifier.pmid22709011-
dc.identifier.urihttp://hdl.handle.net/10033/243651-
dc.description.abstractDiketopiperazines are the smallest cyclic peptides known. 90% of Gram-negative bacteria produce diketopiperazines and they have also been isolated from Gram-positive bacteria, fungi and higher organisms. Biosynthesis of cyclodipeptides can be achieved by dedicated nonribosomal peptide synthetases or by a novel type of synthetases named cyclopeptide synthases. Since the first report in 1924 a large number of bioactive diketopiperazines was discovered spanning activities as antitumor, antiviral, antifungal, antibacterial, antiprion, antihyperglycemic or glycosidase inhibitor agents. As infections are of increasing concern for human health and resistances against existing antibiotics are growing this review focuses on the antimicrobial activities of diketopiperazines. The antibiotic bicyclomycin is a diketopiperazine and structure activity studies revealed the unique nature of this compound which was finally developed for clinical applications. The antimicrobial activities of a number of other diketopiperazines along with structure activity relationships are discussed. Here a special focus is on the activity-toxicity problem of many compounds setting tight limitations to their application as drugs. Not only these classical antimicrobial activities but also proposed action in modulating bacterial communication as a new target to control biofilms will be evaluated. Pathogens organized in biofilms are difficult to eradicate because of the increase of their tolerance for antibiotics for several orders. Diketopiperazines were reported to modulate LuxR-mediated quorum-sensing systems of bacteria, and they are considered to influence cell-cell signaling offering alternative ways of biofilm control by interfering with microbial communication. Concluding the review we will finally discuss the potential of diketopiperazines in the clinic to erase biofilm infections.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to Current medicinal chemistryen_GB
dc.titleAntimicrobial and biofilm inhibiting diketopiperazines.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Center for Infection Research, Chemical Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany. wolf-rainer.abraham@helmholtz-hzi.de.en_GB
dc.identifier.journalCurrent medicinal chemistryen_GB
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