合成并评价一种荧光苯妥英类似物作为潜在的治疗神经病理性疼痛和成像试剂。
Synthesis and biological evaluation of a fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain and imaging agent.
机构信息
Drug Discovery Program, Department of Oncology, Georgetown University Medical Center, 3970 Reservoir Rd., NW, Washington, DC 20057, USA.
出版信息
Bioorg Med Chem. 2012 Sep 1;20(17):5269-76. doi: 10.1016/j.bmc.2012.06.042. Epub 2012 Jul 3.
Abstract
Here we report on a novel fluorescent analog of phenytoin as a potential inhibitor of neuropathic pain with potential use as an imaging agent. Compound 2 incorporated a heptyl side chain and dansyl moiety onto the parent compound phenytoin and produced greater displacement of BTX from sodium channels and greater functional blockade with greatly reduced toxicity. Compound 2 reduced mechano-allodynia in a rat model of neuropathic pain and was visualized ex vivo in sensory neuron axons with two-photon microscopy. These results suggest a promising strategy for developing novel sodium channel inhibitors with imaging capabilities.
摘要
在这里，我们报告了一种新型荧光苯妥英类似物作为治疗神经性疼痛的潜在抑制剂，具有作为成像剂的应用潜力。化合物 2 是在母体化合物苯妥英的基础上引入了庚基侧链和丹磺酰基，与钠离子通道的结合能力更强，功能阻断作用更强，而毒性大大降低。化合物 2 降低了神经性疼痛大鼠模型的机械性痛觉过敏，并通过双光子显微镜在感觉神经元轴突中进行了体外可视化。这些结果表明，开发具有成像功能的新型钠离子通道抑制剂具有很大的潜力。
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