linezolid and ranbezolid

Oxazolidinones are known to inhibit protein biosynthesis and act against a wide spectrum of gram-positive bacteria. A new investigational oxazolidinone, ranbezolid, inhibited bacterial protein synthesis in Staphylococcus aureus and Staphylococcus epidermidis. In S. epidermidis, ranbezolid showed inhibition of cell wall and lipid synthesis and a dose-dependent effect on membrane integrity. A kill-kinetics study showed that ranbezolid was bactericidal against S. epidermidis. In vitro translation of the luciferase gene done using bacterial and mammalian ribosomes indicated that ranbezolid specifically inhibited the bacterial ribosome. Molecular modeling studies revealed that both linezolid and ranbezolid fit in similar manners the active site of ribosomes, with total scores, i.e., theoretical binding affinities after consensus, of 5.2 and 6.9, respectively. The nitrofuran ring in ranbezolid is extended toward C2507, G2583, and U2584, and the nitro group forms a hydrogen bond from the base of G2583. The interaction of ranbezolid with the bacterial ribosomes clearly helps to elucidate its potent activity against the target pathogen.

Topics: Acetamides; Anti-Bacterial Agents; Cell Membrane Permeability; Furans; Linezolid; Oxazoles; Oxazolidinones; Protein Biosynthesis; Protein Synthesis Inhibitors; Ribosomes; Staphylococcus aureus; Staphylococcus epidermidis; Transcription, Genetic

A number of 5-substituted derivatives of Ranbezolid, a novel oxazolidinone were synthesized. Antibacterial activity of the compounds against a number of sensitive and resistant bacteria showed promising results.

Topics: Anti-Bacterial Agents; Bacteria; Drug Design; Furans; Microbial Sensitivity Tests; Oxazoles; Oxazolidinones; Vancomycin Resistance

Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate.

Topics: Animals; Anti-Bacterial Agents; Drug Resistance, Microbial; Furans; Gram-Positive Bacteria; Heterocyclic Compounds; Mice; Microbial Sensitivity Tests; Oxazoles; Oxazolidinones; Staphylococcal Infections; Structure-Activity Relationship