6533b81ffe1ef96bd1277254
RESEARCH PRODUCT
New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens
Carmela BonaccorsoLaura RizziPaola PierroCosimo G. FortunaGianluigi CaltabianoGiuseppe MusumarraClementina CocuzzaLaura GoracciRosario MusumeciAlessandra BulbarelliAnnalisa GuarcelloAntonio Palumbo-piccionelloAndrea Pacesubject
Methicillin-Resistant Staphylococcus aureusModels MolecularCell viabilityStaphylococcus aureusMolecular modelCell SurvivalMicrobial Sensitivity TestsAntimicrobial activityCrystallography X-Raymedicine.disease_causeDrug designMicrobiologyStructure-Activity Relationshipchemistry.chemical_compoundoxadiazoles linezolid antibioticsCell Line TumorDrug Resistance Multiple BacterialMorpholineAcetamidesDrug DiscoverymedicineHumansMoietyStructure–activity relationshipOxazolidinonesPharmacologyOxadiazolesOxazolidinones; Linezolid; Drug designDose-Response Relationship DrugMolecular StructureChemistryOrganic ChemistryLinezolidSettore CHIM/06 - Chimica OrganicaHep G2 CellsGeneral Medicinebiochemical phenomena metabolism and nutritionbacterial infections and mycosesSettore CHIM/08 - Chimica FarmaceuticaMethicillin-resistant Staphylococcus aureusCombinatorial chemistryOxazolidinoneAnti-Bacterial AgentsStaphylococcus aureusMED/07 - MICROBIOLOGIA E MICROBIOLOGIA CLINICALinezolidAntimicrobial activity; Cell viability; Drug design; Oxazolidinones; Staphylococcus aureusAntibacterial activitySoftwaredescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-07-01 |