Preclinical Development of MiBIECT, a New Oxadiazolyl-Oxazolidinone Compound Active against Gram-positive Cocci

Background: MiBIECT is a new oxadiazolyl-oxazolidinone that has been developed by means of chemoinformatic tools, synthesis and biological evaluation. This agent demonstrates potent activity against Gram-positive pathogens, including linezolid-resistant (LZDR) isolates. The aims of this study were to determine the in vitro activity of MiBIECT against a greater number of Gram-positive cocci with various resistant phenotypes, and to evaluate MiBIECT for in vitro cytotoxicity. Methods: A total of 340 strains of linezolid-susceptible (LZD-S) S. aureus, S. epidermidis, enterococci, S. pneumoniae, S. pyogenes and 20 LZDR strains were analyzed. MiBIECT was evaluated for its in vitro antibacterial activity by determining the minimum inhibitory concentrations (MIC) by the CLSI broth microdilution methods. In vitro cytotoxicity assays in cell lines representative of excretory organs were used to evaluate for potential safety concerns. Results: MiBIECT exhibited potent activity against S. aureus, S. epidermidis, S. pneumoniae and S. pyogenes with MICs in range of <0.06 - 1 mcg/mL. MiBIECT MIC values were 2-3 and 4 dilutions lower for LZD-S and LZD-R strains, respectively, compared to linezolid. In vitro cytotoxicity experiments indicated that MIBIECT has a similar effect on cell viability as linezolid with fewer effects on mammalian mitochondrial protein synthesis inhibition. Conclusions: MiBIECT demonstrated potent in vitro activity against Gram-positive bacteria, with little toxicity against various cell lines. The in vitro activity of this investigational agent was maintained against LZDR isolates. Thus, further studies are warranted to determine the potential utility of this agent in the treatment of Gram-positive bacterial infections