NeuroFarba Department, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Italy.
Centre of Advanced Research in Bionanoconjugates and Biopolymers, Petru Poni Institute of Macromolecular Chemistry, Aleea Grigore Ghica-Voda, no. 41A, 700487 Iasi, Romania.
Molecules. 2021 Nov 20;26(22):7023. doi: 10.3390/molecules26227023.
A series of benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with several bulky moieties has been obtained by original procedures. The new derivatives were investigated for the inhibition of four physiologically crucial human carbonic anhydrase (hCA, EC 4.2.2.1.1) isoforms, hCA I and II (cytosolic enzymes) as well as hCA IX and XII (transmembrane, tumor-associated isoforms). Examples of isoform-selective inhibitors were obtained for all four enzymes investigated here, and a computational approach was employed for explaining the observed selectivity, which may be useful in drug design approaches for obtaining inhibitors with pharmacological applications useful as antiglaucoma, diuretic, antitumor or anti-cerebral ischemia drugs.
通过原创方法获得了一系列苯磺酰胺，其中包含了带有多个大体积部分的吡唑和哒嗪甲酰胺。新衍生物被用于抑制四种生理上重要的人碳酸酐酶（hCA，EC 4.2.2.1.1）同工酶，即 hCA I 和 II（细胞质酶）以及 hCA IX 和 XII（跨膜、肿瘤相关同工酶）。对于所有四种研究的酶，都获得了同工酶选择性抑制剂的实例，并且采用了计算方法来解释观察到的选择性，这可能有助于药物设计方法，获得具有药理学应用的抑制剂，如青光眼、利尿剂、抗肿瘤或抗脑缺血药物。
