Design, synthesis and biological evaluation of 5'-C-piperidinyl-5'-O-aminoribosyluridines as potential antibacterial agents
| Autor: | Satoshi Ichikawa, Akira Matsuda, Takeshi Nakaya |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
medicine.drug_class Stereochemistry Antibiotics Molecular Conformation Microbial Sensitivity Tests medicine.disease_cause Biochemistry Vancomycin-Resistant Enterococci Mice Structure-Activity Relationship medicine Structure–activity relationship Animals Humans Physical and Theoretical Chemistry Mode of action Cytotoxicity biology Dose-Response Relationship Drug Chemistry Organic Chemistry Hep G2 Cells biology.organism_classification Combinatorial chemistry Anti-Bacterial Agents Staphylococcus aureus Drug Design Microsomes Liver Azetidines Antibacterial activity Nucleoside Azabicyclo Compounds Bacteria |
| Zdroj: | Organicbiomolecular chemistry. 13(28) |
| ISSN: | 1477-0539 |
| Popis: | The discovery of new antibiotics is critical because the emergence of drug-resistant bacteria has posed a serious public health problem. Caprazamycins, which are nucleoside antibiotics, are a promising lead with a novel mode of action, and we have designed simplified analogues containing a piperidine as a scaffold linking the crucial structural units of caprazamycins. These analogues were step-economically synthesized via a sequential aza-Prins–Ritter reaction. Among the tested compounds, the analogue 7 exhibited good MraY inhibitory activity, antibacterial activity against Gram-positive bacterial strains including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci, and metabolic stability. The observed cytotoxicity of 7 against HepG2 cells was overcome by modulating the fatty acyl side chain. The knowledge obtained from our structure–activity relationship studies of the caprazamycins will provide further direction toward the design of potent MraY inhibitors. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|