title: In Vitro Activities of LCB 01-0648, a Novel Oxazolidinone, against Gram-Positive Bacteria.
abstract: Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistantStaphylococcus aureus(MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC90s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistantS. aureus(LRSA) strains (range 2-4 mg/L). The results of the time-kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptibleStaphylococcus aureusMSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci.
authors.affiliation: School of Life Science, Handong Global University, Pohang 37554, Korea. osh8755@naver.com.
authors.forename: Sang-Hun
authors.initials: SH
authors.lastname: Oh
authors.affiliation: School of Life Science, Handong Global University, Pohang 37554, Korea. indy8152@naver.com.
authors.forename: Josep
authors.initials: J
authors.lastname: Kim
authors.affiliation: LegoChem BioSciences. Inc., Daejeon 34302, Korea. bsy@legochembio.com.
authors.forename: Sung-Yoon
authors.initials: SY
authors.lastname: Baek
authors.affiliation: LegoChem BioSciences. Inc., Daejeon 34302, Korea. sangeun@legochembio.com.
authors.forename: Sang-Eun
authors.initials: SE
authors.lastname: Chae
authors.affiliation: School of Food Science and Biotechnology, Institute of Agricultural Science & Technology, Kyungpook National University, Daegu 41566, Korea. phsoo97@knu.ac.kr.
authors.forename: Hee-Soo
authors.initials: HS
authors.lastname: Park
authors.affiliation: LegoChem BioSciences. Inc., Daejeon 34302, Korea. young@legochembio.com.
authors.forename: Young-Lag
authors.initials: YL
authors.lastname: Cho
authors.affiliation: School of Life Science, Handong Global University, Pohang 37554, Korea. jhkwak@handong.edu.
authors.forename: Jin-Hwan
authors.initials: JH
authors.lastname: Kwak
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D025141:Drug Resistance, Fungal / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D023303:Oxazolidinones
keywords: LCB01-0648; MICs; linezolid-resistant S. aureus; oxazolidinone