Abstract
Pseudomonas aeruginosa is a dangerous opportunistic bacterium responsible for frequently lethal hospital (nosocomial) infections. It endangers especially severely injured patients suffering from large wounds or severe burns, as well as persons whose immune system is weakened. An extremely critical situation exists for patients suffering from mucoviscidosis (cystic fibrosis), when P. aeruginosa infects the bronchial tubes. P. aeruginosa is resistant against many desinfecting agents and, more important, an increasing number of strains especially from hospital isolates have become highly resistant against most antibiotics. The low permeability of the outer membrane and an active export mechanism for low molecular weight substances are the main reasons for the resistance. In addition, b-lactamase activity affects treatment with b-lactam antibiotics. An approach to overcome the problem of resistance lies in the synthesis of antibiotics conjugated with compounds active as siderophores. In this way the transport ways for iron complexes into the cell can be used (Trojan Horse strategy), and the presence of large substituents reduces the export and the b-lactamase activity. The results obtained with natural (pyoverdins) and synthetic (mainly catecholate) siderophores will be reviewed.
Keywords: Siderophore Antibiotic Conjugates, Trojan Horses, Pseudomonas aeruginosa, lactamase, iron regulated outer membrane proteins, PYOVERDIN LACTAM CONJUGATES, SIDEROPHORE-b-LACTAM, Catecholates, Hydroxamates
Current Topics in Medicinal Chemistry
Title: Siderophore-Antibiotic Conjugates Used as Trojan Horses Against Pseudomonas aeruginosa
Volume: 1 Issue: 1
Author(s): Herbert Budzikiewicz
Affiliation:
Keywords: Siderophore Antibiotic Conjugates, Trojan Horses, Pseudomonas aeruginosa, lactamase, iron regulated outer membrane proteins, PYOVERDIN LACTAM CONJUGATES, SIDEROPHORE-b-LACTAM, Catecholates, Hydroxamates
Abstract: Pseudomonas aeruginosa is a dangerous opportunistic bacterium responsible for frequently lethal hospital (nosocomial) infections. It endangers especially severely injured patients suffering from large wounds or severe burns, as well as persons whose immune system is weakened. An extremely critical situation exists for patients suffering from mucoviscidosis (cystic fibrosis), when P. aeruginosa infects the bronchial tubes. P. aeruginosa is resistant against many desinfecting agents and, more important, an increasing number of strains especially from hospital isolates have become highly resistant against most antibiotics. The low permeability of the outer membrane and an active export mechanism for low molecular weight substances are the main reasons for the resistance. In addition, b-lactamase activity affects treatment with b-lactam antibiotics. An approach to overcome the problem of resistance lies in the synthesis of antibiotics conjugated with compounds active as siderophores. In this way the transport ways for iron complexes into the cell can be used (Trojan Horse strategy), and the presence of large substituents reduces the export and the b-lactamase activity. The results obtained with natural (pyoverdins) and synthetic (mainly catecholate) siderophores will be reviewed.
Export Options
About this article
Cite this article as:
Budzikiewicz Herbert, Siderophore-Antibiotic Conjugates Used as Trojan Horses Against Pseudomonas aeruginosa, Current Topics in Medicinal Chemistry 2001; 1 (1) . https://dx.doi.org/10.2174/1568026013395524
DOI https://dx.doi.org/10.2174/1568026013395524 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Adaptogens—History and Future Perspectives
Adaptogens are pharmacologically active compounds or plant extracts that are associated with the ability to enhance the body’s stability against stress. The intake of adaptogens is associated not only with a better ability to adapt to stress and maintain or normalise metabolic functions but also with better mental and physical ...read more
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
![Wayfinder Image](/images/wayfinder.jpg)
- 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
-
Pediatric Oral Lichen Planus: Review and Case Report
Current Pediatric Reviews New Perspective on the Dual Functions of Indirubins in Cancer Therapy and Neuroprotection
Anti-Cancer Agents in Medicinal Chemistry The Role of Cyclic Nucleotides in Compensatory Hepatocyte Proliferation
Current Drug Metabolism Designing a Novel Multi-Epitope Vaccine Against Htlv-1 Related Adult T-cell Leukemia/Lymphoma: An In Silico Approach
Current Proteomics Metal Containing Cytostatics and Their Interaction with Cellular Thiol Compounds Causing Chemoresistance
Anti-Cancer Agents in Medicinal Chemistry Current Status and Future Prospects of Small–molecule Protein–protein Interaction (PPI) Inhibitors of Tumor Necrosis Factor (TNF) and Receptor Activator of NF-κB Ligand (RANKL)
Current Topics in Medicinal Chemistry An Overview of Galenic Preparation Methods for Medicinal Cannabis
Current Bioactive Compounds Proteinase-Activated Receptor 2 (PAR2): A Challenging New Target for Treatment of Vascular Diseases
Current Pharmaceutical Design Endothelial Cell Adhesion Molecules and Cancer Progression
Current Medicinal Chemistry Novel Kynurenic Acid Analogues in the Treatment of Migraine and Neurodegenerative Disorders: Preclinical Studies and Pharmaceutical Design
Current Pharmaceutical Design Radiolabelled Peptides and Monoclonal Antibodies for Therapy Decision Making in Inflammatory Diseases
Current Pharmaceutical Design Canine Nutritional Model: Influence of Age, Diet, and Genetics on Health and Well-Being
Current Nutrition & Food Science Mineralocorticoid Receptor-Associated Hypertension and Target Organ Damage: Clinical Relevance for Resistant Hypertension in End Stage Renal Disease
Current Hypertension Reviews The Role of CXCR2/CXCR2 Ligands in Acute Lung Injury
Current Drug Targets - Inflammation & Allergy Fc Receptors as Potential Targets for the Treatment of Allergy, Autoimmune Disease and Cancer
Current Drug Targets - Immune, Endocrine & Metabolic Disorders CIAPIN1 siRNA Inhibits Proliferation, Migration and Promotes Apoptosis of VSMCs by Regulating Bcl-2 and Bax
Current Neurovascular Research Role of Salt and Potassium in Hypertension and the Associated Organ Damages
Current Hypertension Reviews The Neurovascular Unit: Focus on the Regulation of Arterial Smooth Muscle Cells
Current Neurovascular Research The Current and Future Therapies for Human Osteosarcoma
Current Cancer Therapy Reviews Impact of Interleukin 28B and ICAM-1 Genetic Polymorphisms on Response to Direct Antiviral Treatment Among HCV Infected Patients
Endocrine, Metabolic & Immune Disorders - Drug Targets