Division of Gastroenterology, Department of Internal Medicine, Graduate School of Medicine, Kobe University, Kobe, Hyogo 650-0017, Japan.
Int J Mol Med. 2010 Nov;26(5):751-8. doi: 10.3892/ijmm_00000522.
The sulfonolipid, sulfobacin B, is isolated from Chryseobacterium sp. and functions both as a von Willebrand factor receptor antagonist and a DNA polymerase (pol) α inhibitor. Previously, we chemically synthesized sulfobacin B by starting from L-cysteine. In this study, we investigated the inhibitory effects of chemically synthesized sulfobacin B on the activity of pols and other DNA metabolic enzymes. Sulfobacin B selectively inhibited the activity of all animal pol species: Among the pols tested, the inhibitory effect of the compound on pol λ activity was the strongest with IC50 values of 1.6 µM. However, sulfobacin B did not influence the activity of plant or prokaryotic pols, or that of the other DNA metabolic enzymes such as primase of pol α, RNA polymerase, polynucleotide kinase or deoxyribonuclease I. As we previously found a positive relationship between pol λ inhibition and anti-inflammation, we examined whether sulfobacin B could inhibit inflammatory responses. The compound caused a marked reduction in 12-O-tetradecanoylphorbol-13-acetate-induced acute inflammation in the mouse ear. In a cell culture system using mouse macrophages, sulfobacin B strongly inhibited the production of tumor necrosis factor (TNF)-α and the action of nuclear factor-κB induced by lipopolysaccharide (LPS). In an in vivo mouse model of LPS-induced acute inflammation, the intraperitoneal injection of sulfobacin B to mice led to the suppression of serum TNF-α production. These results indicate that sulfobacin B is a potential chemotherapeutic agent for inflammation.
磺基脂 B 是从鞘氨醇杆菌属中分离出来的，具有作为血管性血友病因子受体拮抗剂和 DNA 聚合酶 (pol)α 抑制剂的双重功能。此前，我们通过 L-半胱氨酸化学合成了磺基脂 B。在这项研究中，我们研究了化学合成的磺基脂 B 对 pol 及其它 DNA 代谢酶活性的抑制作用。磺基脂 B 选择性抑制所有动物 pol 种类的活性：在所测试的 pol 中，该化合物对 pol λ 活性的抑制作用最强，IC50 值为 1.6 µM。然而，磺基脂 B 不影响植物或原核 pol 的活性，也不影响其它 DNA 代谢酶如 pol α 的引物酶、RNA 聚合酶、多核苷酸激酶或脱氧核糖核酸酶 I 的活性。由于我们之前发现 pol λ 抑制与抗炎之间存在正相关关系，因此我们检查了磺基脂 B 是否可以抑制炎症反应。该化合物可显著减少在小鼠耳中 12-O-十四烷酰佛波醇-13-乙酸酯诱导的急性炎症。在使用小鼠巨噬细胞的细胞培养系统中，磺基脂 B 强烈抑制脂多糖 (LPS) 诱导的肿瘤坏死因子 (TNF)-α 的产生和核因子-κB 的作用。在 LPS 诱导的急性炎症的体内小鼠模型中，磺基脂 B 腹腔注射到小鼠体内可抑制血清 TNF-α 的产生。这些结果表明磺基脂 B 是一种有潜力的抗炎化疗药物。
