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.
Keywords: Antimicrobials, antivirals, biofilm inhibitors, cyclic dipeptides, diketopiperazines, fungicides, quorum quenchers
Current Medicinal Chemistry
Title:Antimicrobial and Biofilm Inhibiting Diketopiperazines
Volume: 19 Issue: 21
Author(s): M. P. de Carvalho and W.-R. Abraham
Affiliation:
Keywords: Antimicrobials, antivirals, biofilm inhibitors, cyclic dipeptides, diketopiperazines, fungicides, quorum quenchers
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.
Export Options
About this article
Cite this article as:
P. de Carvalho M. and Abraham W.-R., Antimicrobial and Biofilm Inhibiting Diketopiperazines, Current Medicinal Chemistry 2012; 19 (21) . https://dx.doi.org/10.2174/092986712801323243
DOI https://dx.doi.org/10.2174/092986712801323243 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Serpin Regulation of Fibrinolytic System: Implications for Therapeutic Applications in Cardiovascular Diseases
Cardiovascular & Hematological Agents in Medicinal Chemistry Adverse Events of Proton Pump Inhibitors: Potential Mechanisms
Current Drug Metabolism Association between Antiretroviral Treatment and Markers of Systemic Inflammation among HIV Patients in Ghana
Current HIV Research Pharmacological and Biological Activities of Xanthones
Anti-Infective Agents in Medicinal Chemistry Nitric Oxide-Releasing Biomaterials for Biomedical Applications
Current Medicinal Chemistry Nanotherapeutics in Neuropathologies: Obstacles, Challenges and Recent Advancements in CNS Targeted Drug Delivery Systems
Current Neuropharmacology Myelin Sheaths and Autoimmune Response Induced by Myelin Proteins and Alphaviruses. I. Physicochemical Background
Current Medicinal Chemistry Pharmacogenomics in the Intensive Care Unit: Focus on Potential Implications for Clinical Practice
Recent Patents on Biotechnology Nanoparticulated Nitric Oxide Donors and their Biomedical Applications
Mini-Reviews in Medicinal Chemistry Biotechnology for the Investigation of the Monocyte-Macrophage-System in Microgravity and Space
Recent Patents on Space Technology Evaluation on Clot Buster Activity of Staphylokinase from Staphylococcus sp.
Cardiovascular & Hematological Agents in Medicinal Chemistry Micronutrient Biofortification in Rice through New Breeding Techniques (NBTs): Bangladesh Perspective
Current Nutraceuticals Yeast Network and Report of New Stochastic-Credibility Cell Cycle Models
Current Bioinformatics Involvement of Coagulation and Hemostasis in Inflammatory Bowel Diseases
Current Vascular Pharmacology The Impact of Traditional Chinese Medicine on Mitophagy in Disease Models
Current Pharmaceutical Design TNF-α and Ghrelin: Opposite Effects on Immune System, Metabolism and Mental Health
Protein & Peptide Letters Substance-Related Disorders and Somatic Symptoms: How Should Clinicians Understand the Associations?
Current Drug Abuse Reviews Nutrigenomics and Its Approaches for Control of Chronic Diseases
Current Biotechnology Novel Second Generation HIV Integrase Inhibitor-DOLUTEGRAVIR: An Emerging Weapon Against HIV
Letters in Drug Design & Discovery The Need for Diagnostic Criteria in Systemic Vasculitis
Current Immunology Reviews (Discontinued)