Chérigo Lilia, Pereda-Miranda Rogelio, Gibbons Simon
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510DF, Mexico.
Phytochemistry. 2009 Jan;70(2):222-7. doi: 10.1016/j.phytochem.2008.12.005. Epub 2009 Jan 10.
As part of an ongoing project to identify oligosaccharides which modulate bacterial multidrug resistance, the CHCl(3)-soluble extract from flowers of a Mexican arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded five lipophilic tetrasaccharide inhibitors of Staphylococcusaureus multidrug efflux pumps, murucoidins XII-XVI (1-5). The macrocyclic lactone-type structures for these linear hetero-tetraglycoside derivatives of jalapinolic acid were established by spectroscopic methods. These compounds were tested for in vitro antibacterial and resistance modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. Only murucoidin XIV (3) displayed antimicrobial activity against SA-1199B (MIC 32microg/ml), a norfloxacin-resistant strain that over-expresses the NorA MDR efflux pump. The four microbiologically inactive (MIC>512microg/ml) tetrasaccharides increased norfloxacin susceptibility of this strain by 4-fold (8microg/ml from 32microg/ml) at concentrations of 25microg/ml, while murucoidin XIV (3) exerted the same potentiation effect at a concentration of 5microg/ml.
作为一项正在进行的旨在鉴定可调节细菌多药耐药性的寡糖的项目的一部分，通过制备规模循环高效液相色谱法，从墨西哥乔木状牵牛（Ipomoea murucoides）的花朵中提取的氯仿可溶提取物，得到了五种亲脂性四糖抑制剂，即murucuoidins XII-XVI（1-5），它们可抑制金黄色葡萄球菌的多药外排泵。通过光谱方法确定了这些加拉皮诺酸线性杂四糖苷衍生物的大环内酯型结构。对这些化合物针对具有多药耐药外排机制的金黄色葡萄球菌菌株进行了体外抗菌和耐药性修饰活性测试。只有murucuoidin XIV（3）对SA-1199B（MIC 32μg/ml）显示出抗菌活性，SA-1199B是一种耐诺氟沙星的菌株，其过度表达NorA多药耐药外排泵。四种无微生物活性（MIC>512μg/ml）的四糖在浓度为25μg/ml时，可使该菌株对诺氟沙星的敏感性提高4倍（从32μg/ml降至8μg/ml），而murucuoidin XIV（3）在浓度为5μg/ml时发挥相同的增效作用。
