Daniel Łowicki

Structure and Antimicrobial Properties of Monensin A and Its Derivatives: Summary of the Achievements

In this paper structural and microbiological studies on the ionophorous antibiotic monensin A and its derivatives have been collected. Monensin A is an ionophore which selectively complexes and transports sodium cation across lipid membranes, and therefore it shows a variety of biological properties. This antibiotic is commonly used as coccidiostat and nonhormonal growth promoter. The paper focuses on both the latest and earlier achievements concerning monensin A antimicrobial activity. The activities of monensin derivatives, including modifications of hydroxyl groups and carboxyl group, are also presented.

Monensin A acid complexes as a model of electrogenic transport of sodium cation.

New Monensin A acid complexes with water molecule, sodium chloride and sodium perchlorate were obtained and studied by X-ray and (1)H, (13)C NMR and FT-IR methods as well as ab initio calculations. The crystal structure of the complexes indicates the complexation of the water molecule and Na(+) cation in the pseudo-cycle conformation of the Monensin acid molecule stabilised by intramolecular hydrogen bonds. Important for stabilisation of this structure is also the intermolecular hydrogen bonds with water molecule or the coordination bonds with Na(+) cation. It is demonstrated that the counterions forming intermolecular hydrogen bonds with OH groups influence the strength of the intramolecular hydrogen bonds, but they have no influence on the formation of pseudo-cyclic structure. Spectroscopic studies of the complexes in dichloromethane solution have shown that the pseudo-cyclic structure of the compounds is conserved. As follows from the ab initio calculations, the interactions between the Na(+) cation and the electronegative oxygen atoms of Monensin acid totally change the molecular electrostatic potential around the supramolecular Monensin acid-Na(+) cationic complex relative to that of the neutral Monensin acid molecule.

Structural characterization and antibacterial activity against clinical isolates of Staphylococcus of N-phenylamide of monensin A and its 1:1 complexes with monovalent cations.

The ability of N-phenylamide of monensin A (M-AM1) to form complexes with Li(+), Na(+) and K(+) cations is studied by ESI MS, (1)H and (13)C NMR, FT-IR spectroscopy and PM5 semi-empirical methods. ESI mass spectrometry indicates that M-AM1 forms complexes with the Li(+), Na(+) and K(+) cations of exclusively 1:1 stoichiometry which are stable up to cv = 90 V, and the formation of the complex with the Na(+) cation is strongly favoured. In the ESI MS spectra measured at cv = 110 V the fragmentation of the respective complexes, involving several dehydration steps, is observed. The spectroscopic studies show that the structures of M-AM1 and its complexes with Li(+), Na(+) and K(+) cations are stabilized by intramolecular hydrogen bonds in which OH groups are always involved. The CO amide group is shown to be engaged in the complexation process of each cation. However, there is a complex with K(+) cation in whose structure this CO amide group does not participate to a significant extent. The in vitro biological tests of M-AM1 amide have proved its good activity towards some strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE).