Search results for " Linezolid"
showing 8 items of 8 documents
Asymmetric synthesis and biological evaluation of 1,2,4-Oxadiazoles analogues of Linezolid
2014
Oxazolidinones are a class of antibacterial agents which displayed activity againist a variety of gram-positive pathogens and are highly potent against multidrug-resistant bacteria. Linezolid is the first oxazolidinone antibiotic approved for clinical use but linezolid resistance began to appear. 1,2,4 – Oxadiazoles are known bioactive heterocycles whose activity has been often associated to their bioisosterism with amide or ester functionalities [1]. As results of a research project on the molecular design of heterocycle – based antibacterials to contrast Multi-Drug Resistance (MDR) [2], we report the synthesis of 1,2,4 - Oxadiazole analogues of Linezolid. The synthesis has been achieved b…
New linezolid-like 1,2,4-oxadiazoles active against Gram-positive multiresistant pathogens
2013
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…
New potent antibacterials against Gram-positive multiresistant pathogens: effects of side chain modification and chirality in linezolid-like 1,2,4-ox…
2014
The effects of side chain modification and chirality in linezolid-like 1,2,4-oxadiazoles have been studied to design new potent antibacterials against Gram-positive multidrug-resistant pathogens. The adopted strategy involved a molecular modelling approach, the synthesis and biological evaluation of new designed compounds, enantiomers separation and absolute configuration assignment. Experimental determination of the antibacterial activity of the designed (S)-1-((3-(4-(3-methyl-1,2,4-oxadiazol-5- yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea and (S)-1-((3-(3-fluoro-4-(3-methyl-1,2,4- oxadiazol-5-yl)phenyl)-oxazolidin-2-one-5-yl)methyl)-3-methylthiourea against multidrug resistan…
Concise asymmetric synthesis of Linezolid through catalyzed Henry reaction
2013
A new asymmetric synthesis of the antibiotic Linezolid was performed through a copper-catalyzed Henry reaction as the key step. The use of camphor-derived aminopyridine ligands helped to improve the yields of the chiral precursor and to obtain Linezolid in good overall yield and enantiomeric excess.
Synthesis and biological evaluation of 1,4-oxadiazole analogues of Linezolid
2012
Sintesi di 1,2,4-ossadiazoli fluorurati analoghi del Linezolid come potenziali anti-batterici
2009
L'aumentata multidrug resistance tra i batteri patogeni Gram-positivi ha riacceso l'interesse verso la ricerca di nuove classi strutturali di antibiotici attivi nei confronti di batteri multiresistenti.1 Il Linezolid, appartenente alla classe degli ossazolidinoni, è il capostipite di una nuova generazione di anti-batterici di sintesi attivi contro patogeni Gram-positivi.2 La ricerca di nuovi analoghi del Linezolid risulta quanto mai attuale dato il recente riscontro di fenomeni di resistenza batterica a tale farmaco.3 In questo contesto, verranno presentati alcuni risultati preliminari relativi allo sviluppo di nuove metodologie di sintesi per l’ottenimento di composti eterociclici fluorura…
Sintesi e valutazione biologica di 1,2,4-ossadiazoli analoghi del Linezolid
2011
Synthesis and preliminary antibacterial evaluation of Linezolid-like 1,2,4-oxadiazole derivatives
2012
In the present study the synthesis of new Linezolid-like molecules has been achieved by substitution of the oxazolidinone central heterocyclic moiety with a 1,2,4-oxadiazole ring. Two series of 1,2,4-oxadiazoles, bearing different side-chains and containing a varying number of fluorine atoms, were synthesized and preliminarily tested for biological activity against some Gram-positive and Gram-negative bacteria using Linezolid and Ceftriaxone as reference drugs