1. Inhibitors of bacterial multidrug efflux pumps from the resin glycosides of Ipomoea murucoides.
- Author
-
Chérigo L, Pereda-Miranda R, Fragoso-Serrano M, Jacobo-Herrera N, Kaatz GW, and Gibbons S
- Subjects
- Anti-Bacterial Agents chemistry, Carbohydrate Sequence, Chromatography, High Pressure Liquid, Fatty Acids chemistry, Glycosides chemistry, Membrane Transport Proteins drug effects, Mexico, Molecular Structure, Nuclear Magnetic Resonance, Biomolecular, Resins, Plant chemistry, Staphylococcus aureus genetics, Staphylococcus aureus metabolism, Anti-Bacterial Agents isolation & purification, Anti-Bacterial Agents pharmacology, Drug Resistance, Multiple, Bacterial, Fatty Acids isolation & purification, Glycosides isolation & purification, Ipomoea chemistry, Membrane Transport Proteins metabolism, Plants, Medicinal chemistry, Resins, Plant isolation & purification, Staphylococcus aureus drug effects
- Abstract
A reinvestigation of the CHCl 3-soluble extract from flowers of the Mexican medicinal arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded six new pentasaccharides, murucoidins VI-XI (1- 6), as well as the known pescaprein III (7), stoloniferin I (8), and murucoidins I-V (9- 13). Their structures were characterized through the interpretation of their NMR spectroscopic and FABMS data. Compounds 1-6 were found to be macrolactones of three known glycosidic acids identified as simonic acids A and B, and operculinic acid A, with different fatty acids esterifying the same positions, C-2 on the second rhamnose unit and C-4 on the third rhamnose moiety. The lactonization site of the aglycone was placed at C-2 or C-3 of the second saccharide unit. The esterifying residues were composed of two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids, and two long-chain fatty acids, n-dodecanoic (lauric) acid and the new (8R)-(-)-8-hydroxydodecanoic acid. For the latter residue, its absolute configuration was determined by analysis of its Mosher ester derivatives. All members of the murucoidin series exerted a potentiation effect of norfloxacin against the NorA overexpressing Staphylococcus aureus strain SA-1199B by increasing the activity 4-fold (8 microg/mL from 32 microg/mL) at concentrations of 5-25 microg/mL. Stoloniferin I (8) enhanced norfloxacin activity 8-fold when incorporated at a concentration of 5 microg/mL. Therefore, this type of amphipathic oligosaccharide could be developed further to provide more potent inhibitors of this multidrug efflux pump.
- Published
- 2008
- Full Text
- View/download PDF