Inhibitors of bacterial multidrug efflux pumps from the resin glycosides of Ipomoea murucoides.
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.
Chérigo
Lilia
L
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510 DF, Mexico.
Pereda-Miranda
Rogelio
R
Fragoso-Serrano
Mabel
M
Jacobo-Herrera
Nadia
N
Kaatz
Glenn W
GW
Gibbons
Simon
S
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002240:Carbohydrate Sequence; D002851:Chromatography, High Pressure Liquid; D024901:Drug Resistance, Multiple, Bacterial; D005227:Fatty Acids / Q000737:chemistry / Q000302:isolation & purification*; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification*; D027741:Ipomoea / Q000737:chemistry*; D026901:Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D008800:Mexico; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010946:Plants, Medicinal / Q000737:chemistry*; D012116:Resins, Plant / Q000737:chemistry / Q000302:isolation & purification*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D000900:Anti-Bacterial Agents; D005227:Fatty Acids; D006027:Glycosides; D026901:Membrane Transport Proteins; D012116:Resins, Plant