Centre for Systems Chemistry, Stratingh Institute for Chemistry, University of Groningen, Nijenborgh 4, 9747 AG Groningen, The Netherlands.
J Med Chem. 2013 Jun 13;56(11):4456-64. doi: 10.1021/jm400115k. Epub 2013 May 15.
Allergic reactions affect millions of people worldwide. The need for new and effective antiallergic agents is evident, and insight into the underlying mechanisms that lead to allergic events is necessary. Herein, we report the design, synthesis, and activity of photoswitchable mast cell activation inhibitors. In mast cell degranulation assays, these inhibitors possess significantly greater potency than an original, chromone-based antiallergic agent. Furthermore, one of the photoswitchable inhibitors shows a significant difference in inhibitory activity between its two photoisomeric forms. Further optimization could ultimately lead to a photoswitchable compound suitable for studying mechanisms involved in allergic reactions in a novel manner, with activity addressable by light and with precise spatiotemporal control over events at the molecular level.
过敏反应影响着全球数百万人。显然，我们需要新的、有效的抗过敏药物，也需要深入了解导致过敏反应的潜在机制。在此，我们报告了可光开关的肥大细胞激活抑制剂的设计、合成和活性。在肥大细胞脱颗粒测定中，这些抑制剂的活性比原始的基于色酮的抗过敏药物高得多。此外，其中一种可光开关的抑制剂在其两种光异构体形式之间表现出显著的抑制活性差异。进一步的优化最终可能会得到一种适合以新颖的方式研究过敏反应相关机制的可光开关化合物，其活性可通过光来控制，并可在分子水平上对事件进行精确的时空控制。
