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

• Published in: Journal of antibiotics Vol. 64; no. 3; pp. 249 - 256
• Main Authors: Huczyński, Adam, Ratajczak-Sitarz, Małgorzata, Stefańska, Joanna, Katrusiak, Andrzej, Brzezinski, Bogumil, Bartl, Franz
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2011; Japan Antibiotics Research Assoc; Nature Publishing Group
• Subjects: 631/326/22/1290; 631/45/535; 631/92/436/2388; Antibiotic resistance; Bacteriology; Biomedical and Life Sciences; Bioorganic Chemistry; Biotechnology & Applied Microbiology; Carbonyl compounds; Cross Infection - drug therapy; Cross Infection - microbiology; Crystallography, X-Ray; Crystals; Humans; Immunology; Life Sciences; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Medicinal Chemistry; Methicillin Resistance; Microbial Sensitivity Tests; Microbiology; Monensin - analogs & derivatives; Monensin - chemistry; Monensin - pharmacology; Monensin - therapeutic use; Organic Chemistry; original-article; Pharmacology & Pharmacy; Phenylcarbamates - chemistry; Science & Technology; Sodium; Staphylococcal Infections - drug therapy; Staphylococcal Infections - microbiology; Staphylococcus aureus - drug effects; Staphylococcus epidermidis - drug effects; Urethane - chemistry; MRSE; activity; urethanes; polyether antibiotics; structure; MRSA; ANTIBIOTICS; MOLECULAR-STRUCTURE; MONOVALENT CATIONS; CHROMATOGRAPHY; N-PHENYLAMIDE; STAPHYLOCOCCUS; TRANSPORT; 1/1 INCLUSION COMPLEX; ACETONITRILE; METAL-IONS
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2010.167

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.