Liu Mei-Hua, Otsuka Nao, Noyori Kumiko, Shiota Sumiko, Ogawa Wakano, Kuroda Teruo, Hatano Tsutomu, Tsuchiya Tomofusa
Department of Molecular Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan.
Biol Pharm Bull. 2009 Mar;32(3):489-92. doi: 10.1248/bpb.32.489.
In a previous study, we reported that two kaempferol glycosides isolated from Laurus nobilis L., kaempferol-3-O-alpha-L-(2'',4''-di-E-p-coumaroyl)-rhamnoside (C2) and kaempferol-3-O-alpha-L-(2''-E-p-coumaroyl-4''-Z-p-coumaroyl)-rhamnoside (C3), showed strong antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci. Thereafter we found that these compounds greatly reduced the minimum inhibitory concentrations (MICs) of some fluoroquinolones in MRSA. In other words, C2 and C3 greatly potentiated anti-MRSA activity of fluoroquinolones. The effect of C2 and C3 with fluoroquinolones was found to be synergistic. The potentiation activity was observed with hydrophilic fluoroquinolones, such as norfloxacin and ciprofloxacin, but not with hydrophobic quinolones. We also found that norfloxacin reduced MICs of C2 and C3. The effect was synergistic. Possible mechanism of the synergistic effect was discussed.
在之前的一项研究中,我们报道了从月桂叶中分离出的两种山奈酚糖苷,即山奈酚-3-O-α-L-(2'',4''-二-E-p-香豆酰基)-鼠李糖苷(C2)和山奈酚-3-O-α-L-(2''-E-p-香豆酰基-4''-Z-p-香豆酰基)-鼠李糖苷(C3),对耐甲氧西林金黄色葡萄球菌(MRSA)和耐万古霉素肠球菌表现出强大的抗菌活性。此后,我们发现这些化合物大大降低了MRSA中某些氟喹诺酮类药物的最低抑菌浓度(MIC)。换句话说,C2和C3极大地增强了氟喹诺酮类药物的抗MRSA活性。发现C2和C3与氟喹诺酮类药物的作用是协同的。亲水性氟喹诺酮类药物,如诺氟沙星和环丙沙星,观察到了增强活性,但疏水性喹诺酮类药物则没有。我们还发现诺氟沙星降低了C2和C3的MIC。这种作用是协同的。讨论了协同作用的可能机制。