新型喹啉类 Panx-1 通道阻断剂的设计、合成及药理学评价。

Neurofarba, Pharmaceutical and Nutraceutical Section, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.

Department of Industrial Engineering, University of Florence, Via S. Marta 3, 50136 Florence, Italy.

Int J Mol Sci. 2023 Jan 19;24(3):2022. doi: 10.3390/ijms24032022.

Pannexins are an interesting new target in medicinal chemistry, as they are involved in many pathologies such as epilepsy, ischemic stroke, cancer and Parkinson's disease, as well as in neuropathic pain. They are a family of membrane channel proteins consisting of three members, Panx-1, Panx-2 and Panx-3, and are expressed in vertebrates. In the present study, as a continuation of our research in this field, we report the design, synthesis and pharmacological evaluation of new quinoline-based Panx-1 blockers. The most relevant compounds and show an IC = 3 and 1.5 µM, respectively, and are selective Panx-1 blockers. Finally, chemical stability, molecular modelling and X-ray crystallography studies have been performed providing useful information for the realization of the project.

质膜通道蛋白 Pannexin 是医学化学中一个有趣的新靶点，因为它们与多种病理学相关，如癫痫、缺血性中风、癌症和帕金森病，以及神经性疼痛。它们由三个成员 Panx-1、Panx-2 和 Panx-3 组成，存在于脊椎动物中。在本研究中，作为我们在该领域研究的延续，我们报告了新的基于喹啉的 Panx-1 阻断剂的设计、合成和药理学评价。最相关的化合物和分别显示出 IC = 3 和 1.5 µM 的抑制活性，并且是选择性的 Panx-1 阻断剂。最后，进行了化学稳定性、分子建模和 X 射线晶体学研究，为该项目的实施提供了有用的信息。