New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens
| Autor: | Carmela Bonaccorso, Laura Rizzi, Paola Pierro, Cosimo G. Fortuna, Gianluigi Caltabiano, Giuseppe Musumarra, Clementina Cocuzza, Laura Goracci, Rosario Musumeci, Alessandra Bulbarelli, Annalisa Guarcello, Antonio Palumbo Piccionello, Andrea Pace |
|---|---|
| Přispěvatelé: | Fortuna, C, Bonaccorso, C, Bulbarelli, A, Caltabiano, G, Rizzi, L, Goracci, L, Musumarra, G, Pace, A, Palumbo Piccionello, A, Guarcello, A, Pierro, P, Cocuzza, C, Musumeci, R, Fortuna, CG, Cocuzza, CEA |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Methicillin-Resistant Staphylococcus aureus
Models Molecular Cell viability Staphylococcus aureus Molecular model Cell Survival Microbial Sensitivity Tests Antimicrobial activity Crystallography X-Ray medicine.disease_cause Drug design Microbiology Structure-Activity Relationship chemistry.chemical_compound oxadiazoles linezolid antibiotics Cell Line Tumor Drug Resistance Multiple Bacterial Morpholine Acetamides Drug Discovery medicine Humans Moiety Structure–activity relationship Oxazolidinones Pharmacology Oxadiazoles Linezolid Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Settore CHIM/06 - Chimica Organica Hep G2 Cells General Medicine biochemical phenomena metabolism and nutrition bacterial infections and mycoses Settore CHIM/08 - Chimica Farmaceutica Methicillin-resistant Staphylococcus aureus Combinatorial chemistry Oxazolidinone Anti-Bacterial Agents MED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICA Antibacterial activity Software |
| Popis: | The synthesis and the in vitro antibacterial activity of novel linezolid-like oxadiazoles are reported. Replacement of the linezolid morpholine C-ring with 1,2,4-oxadiazole results in an antibacterial activity against Staphylococcus aureus both methicillin-susceptible and methicillin-resistant comparable or even superior to that of linezolid. While acetamidomethyl or thioacetoamidomethyl moieties in the C(5) side-chain are required, fluorination of the phenyl B ring exhibits a slight effect on an antibacterial activity but its presence seems to reduce the compounds cytotoxicity. Molecular modeling performed using two different approaches - FLAP and Amber software - shows that in the binding pose of the newly synthesized compounds as compared with the crystallographic pose of linezolid, the 1,2,4-oxadiazole moiety seems to perfectly mimic the function of the morpholinic ring, since the H-bond interaction with U2585 is retained. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|