Section of Pharmaceutical and Nutraceutical Sciences, Department of Neuroscience, Psychology, Drug Research and Child's Health (Neurofarba), University of Florence, Sesto Fiorentino, Italy.
Department of Pharmacy, University of Pisa, Pisa, Italy.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):48-57. doi: 10.1080/14756366.2020.1838501.
The synthesis and carbonic anhydrase (CA; EC 4.2.1.1) activating effects of a series of oxime ether-based amino alcohols towards four human (h) CA isoforms expressed in human brain, hCA I, II, IV and VII, are described. Most investigated amino alcohol derivatives induced a consistent activation of the tested CAs, with Ks spanning from a low micromolar to a medium nanomolar range. Specifically, hCA II and VII, putative main CA targets when central nervous system (CNS) diseases are concerned, were most efficiently activated by these oxime ether derivatives. Furthermore, a multitude of selective hCA VII activators were identified. As hCA VII is one of the key isoforms involved in brain metabolism and other brain functions, the identified potent and selective hCA VII activators may be considered of interest for investigations of various therapeutic applications or as lead compounds in search of even more potent and selective CA activators.
描述了一系列肟醚基氨基醇对在人脑中共表达的四种人（h）碳酸酐酶（CA；EC 4.2.1.1）的合成和激活作用，hCA I、II、IV 和 VII。大多数研究的氨基醇衍生物对测试的 CA 均表现出一致的激活作用，Ks 范围从低微摩尔到中纳摩尔。具体而言，hCA II 和 VII 是中枢神经系统（CNS）疾病相关的主要 CA 靶标，这些肟醚衍生物对其的激活作用最为有效。此外，还鉴定出了多种选择性 hCA VII 激活剂。由于 hCA VII 是参与大脑代谢和其他大脑功能的关键同工酶之一，因此，所鉴定的有效且选择性的 hCA VII 激活剂可能被认为对各种治疗应用的研究或作为寻找更有效和选择性 CA 激活剂的先导化合物具有重要意义。
