Inhibitors of Bacterial Multidrug Efflux Pumps from the Resin Glycosides of Ipomoea murucoides
详细信息 查看全文
- 作者：Lilia Ché ; rigo ; Rogelio Pereda-Miranda ; Mabel Fragoso-Serrano ; Nadia Jacobo-Herrera ; Glenn W. Kaatz ; Simon Gibbons
- 刊名：Journal of Natural Products
- 出版年：2008
- 出版时间：June 2008
- 年：2008
- 卷：71
- 期：6
- 页码：1037 - 1045
- 全文大小：146K
- 年卷期：v.71,no.6(June 2008)
- ISSN：1520-6025
文摘
A reinvestigation of the CHCl3-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 µg/mL from 32 µg/mL) at concentrations of 5−25 µg/mL. Stoloniferin I (8) enhanced norfloxacin activity 8-fold when incorporated at a concentration of 5 µg/mL. Therefore, this type of amphipathic oligosaccharide could be developed further to provide more potent inhibitors of this multidrug efflux pump.