Ainge Gary D, Hudson Jennifer, Larsen David S, Painter Gavin F, Gill Gurmit Singh, Harper Jacquie L
Industrial Research Limited, Lower Hutt, New Zealand.
Bioorg Med Chem. 2006 Aug 15;14(16):5632-42. doi: 10.1016/j.bmc.2006.04.037. Epub 2006 May 11.
Phosphatidylinositol mannoside (PIM) extracts from mycobacteria have been shown previously to suppress allergic airway inflammation in mice. To help determine the structural requirements for activity, PIM1(2) (1), PIM1(6) (2) and PIM2 (3) were synthesized and tested for their ability to suppress cellular inflammation in a mouse model of allergic asthma. The synthetic PIMs were all effective in suppressing airway eosinophilia in the asthma model, with PIM1(6) being the most effective. Suppression of all inflammatory cells monitored was observed, indicating a general blockade of cellular inflammation. Non-mannosylated phosphatidylinositol (PI) had no suppressive effect, indicating that at least one alpha-d-mannopyranosyl residue is necessary for activity. The suppressive effect of the three PIM compounds indicates that other members of this set may be of value in treatment of a range of diseases driven by infiltration of inflammatory cells.
先前已证明，分枝杆菌的磷脂酰肌醇甘露糖苷（PIM）提取物可抑制小鼠的过敏性气道炎症。为了确定活性的结构要求，合成了PIM1(2)（1）、PIM1(6)（2）和PIM2（3），并在过敏性哮喘小鼠模型中测试它们抑制细胞炎症的能力。合成的PIM在哮喘模型中均能有效抑制气道嗜酸性粒细胞增多，其中PIM1(6)最为有效。观察到对所有监测的炎症细胞均有抑制作用，表明对细胞炎症有普遍的阻断作用。非甘露糖基化磷脂酰肌醇（PI）没有抑制作用，这表明至少一个α-D-甘露吡喃糖基残基是活性所必需的。这三种PIM化合物的抑制作用表明，该系列的其他成员可能对治疗一系列由炎症细胞浸润驱动的疾病有价值。
