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Synthesis of 2,3,6-trideoxy sugar triazole hybrids as potential new broad spectrum antimicrobial agents
- Source :
- European Journal of Medicinal Chemistry. 83:474-489
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Here, we describe a molecular hybridization inspired design and synthesis of novel 6-triazolyl 2,3,6-trideoxy sugars as promising new broad-spectrum antimicrobial agents using click chemistry in key step. These compounds showed MIC between 0.39 and 50 μg/mL against different native and resistant bacteria and fungi with no toxicity. Among them, compound 29 was the most active molecule with MIC 0.78 μg/mL against Staphylococcus aureus and Klebsiella pneumoniae and 3.12 μg/mL against methicillin- and vancomycin-resistant S. aureus. Compound 26 was the most potent anti-fungal candidate with MIC 0.39 μg/mL against Trichophyton mentagrophytes. Compound 46 was found to be promising with broad-spectrum activity against both bacterial and fungal strains. The bioinformatic studies involving bacteria's protein co-crystals prompted penicillin binding protein-2 as the most likely target of these compounds.
- Subjects :
- Models, Molecular
Penicillin binding proteins
Klebsiella pneumoniae
Carbohydrates
Triazole
Chemistry Techniques, Synthetic
Microbial Sensitivity Tests
medicine.disease_cause
Cell Line
Microbiology
chemistry.chemical_compound
Anti-Infective Agents
Catalytic Domain
Drug Discovery
medicine
Penicillin-Binding Proteins
Trichophyton
Pharmacology
Bacteria
biology
Chemistry
Organic Chemistry
Fungi
General Medicine
Triazoles
biology.organism_classification
Antimicrobial
Biochemistry
Staphylococcus aureus
Drug Design
Click Chemistry
Penicillin binding
Subjects
Details
- ISSN :
- 02235234
- Volume :
- 83
- Database :
- OpenAIRE
- Journal :
- European Journal of Medicinal Chemistry
- Accession number :
- edsair.doi.dedup.....8b5265a6861bb1aba47175396b44084b
- Full Text :
- https://doi.org/10.1016/j.ejmech.2014.06.048