title: Reinvestigation of the structure of monensin A phenylurethane sodium salt based on X-ray crystallographic and spectroscopic studies, and its activity against hospital strains of methicillin-resistant S. epidermidis and S. aureus.
abstract: Monensin A phenylurethane sodium salt (MON-UR1-Na) crystals were studied by the X-ray, NMR, FT-IR and PM5 semi-empirical methods. The X-ray data show that the compound forms a pseudocyclic structure, stabilized by three intramolecular hydrogen bonds, and the sodium cation coordinated by five oxygen atoms in the hydrophilic sphere. The NMR and FT-IR data demonstrate that this pseudocyclic structure is also conserved in CH(2)Cl(2) solution. This structure of MON-UR1-Na is significantly different than the ones previously proposed by Westley et al. and Tanaka et al. The semi-empirical calculations of the MON-UR1-Na structures indicate that the one of the crystal is the most energetically favorable one. Other parameters, such as the size, chemical and biological nature of the urethane substituent, and especially the free carbonyl urethane group, may have a role in the biological activity of MON-UR1-Na. The in vitro microbiological tests provide evidence that MON-UR1-Na shows higher antibacterial activity against human pathogenic bacteria, including antibiotic-resistant Staphylococcus aureus and Staphylococcus epidermidis than the parent unmodified antibiotic-Monensin A.
authors.affiliation: Faculty of Chemistry, Adam Mickiewicz University, Poznan, Poland. adhucz@amu.edu.pl
authors.forename: Adam
authors.initials: A
authors.lastname: Huczyński
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Ratajczak-Sitarz
authors.forename: Joanna
authors.initials: J
authors.lastname: Stefańska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Katrusiak
authors.forename: Bogumil
authors.initials: B
authors.lastname: Brzezinski
authors.forename: Franz
authors.initials: F
authors.lastname: Bartl
mesh_terms: D003428:Cross Infection / Q000188:drug therapy / Q000382:microbiology; D018360:Crystallography, X-Ray; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D008985:Monensin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D048448:Phenylcarbamates / Q000737:chemistry; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects*; D013212:Staphylococcus epidermidis / Q000187:drug effects*; D014520:Urethane / Q000737:chemistry
chemical_list: D048448:Phenylcarbamates; D014520:Urethane; D008985:Monensin; C008866:phenylurethane