Department of Pharmaceutical and Applied Chemistry, University of Siena, Via Aldo Moro, 2-53100 Siena, Italy.
J Nat Prod. 2011 Oct 28;74(10):2257-60. doi: 10.1021/np100761u. Epub 2011 Sep 21.
The increasing therapeutic failures against Helicobacter pylori infection has determined the need to develop new drugs. The susceptibility to resveratrol (1) of twenty-six H. pylori strains representing nine CagA+ strains from patients with gastric carcinoma and eight CagA- and nine CagA+ strains from patients with chronic gastritis only was evaluated. Compound 1 was dissolved in DMSO and double diluted in Brucella broth with 10% BFS; ca. 10(6) organisms were added to each dilution. After incubation, subcultures were performed using Columbia-blood agar plates. The lowest concentration in broth at which all the organisms were killed was considered the minimum bactericidal concentration (MBC). Tests were performed in triplicate. The mean MBC of 1 for CagA positive GC strains was significantly lower than those for both CagA positive and CagA negative CG strains. An F1 ATPase of H. pylori showed a significant linear homology with a human ATPase considered a possible target of 1. It was hypothesized that strains infecting patients with gastric carcinoma have a reduced expression of F-type ATPases, which normally protect the bacteria from low pH levels by maintaining a proton gradient across membranes. Such behavior can be considered as an adaptive response to decreased gastric acidity. Since the targets of resveratrol (1) are also the bacterial ATPases, their putative reduced expression could increase the susceptibility to this compound, so that it saturates its targets more quickly and efficiently.
幽门螺杆菌感染的治疗失败率不断上升，这促使人们需要开发新的药物。本研究评估了 26 株幽门螺杆菌菌株对白藜芦醇（1）的敏感性，这 26 株菌株代表了 9 株来自胃癌患者的 CagA+菌株、8 株 CagA-菌株和 9 株 CagA+菌株。化合物 1 溶解在 DMSO 中，并在含有 10% BFS 的 Brucella 肉汤中进行两倍稀释；每个稀释液中加入约 10(6)个细菌。孵育后，使用哥伦比亚血琼脂平板进行亚培养。所有细菌均被杀灭的肉汤中最低浓度被认为是最低杀菌浓度（MBC）。试验重复进行 3 次。CagA 阳性 GC 菌株的 1 的平均 MBC 明显低于 CagA 阳性和 CagA 阴性 CG 菌株。幽门螺杆菌的 F1 型 ATP 酶与人的 ATP 酶具有显著的线性同源性，后者被认为是 1 的可能靶点。据推测，感染胃癌患者的菌株表达的 F 型 ATP 酶减少，这通常通过在膜之间维持质子梯度来保护细菌免受低 pH 值的影响。这种行为可以被认为是对胃酸减少的适应性反应。由于白藜芦醇（1）的靶标也是细菌的 ATP 酶，其表达减少可能会增加对该化合物的敏感性，从而使其更快、更有效地饱和其靶标。
