Monothiocarbamates Strongly Inhibit Carbonic Anhydrases in Vitro and Possess Intraocular Pressure Lowering Activity in an Animal Model of Glaucoma
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- 作者：Daniela Vullo ; Mariaconcetta Durante ; Francesco Saverio Di Leva ; Sandro Cosconati ; Emanuela Masini ; Andrea Scozzafava ; Ettore Novellino ; Claudiu T. Supuran ; Fabrizio Carta
- 刊名：Journal of Medicinal Chemistry
- 出版年：2016
- 出版时间：June 23, 2016
- 年：2016
- 卷：59
- 期：12
- 页码：5857-5867
- 全文大小：583K
- 年卷期：0
- ISSN：1520-4804
文摘
A series of monothiocarbamates (MTCs) were prepared from primary/secondary amines and COS as potential carbonic anhydrase (CA, EC 4.2.1.1) inhibitors, using the dithiocarbamates, the xanthates, and the trithiocarbonates as lead compounds. The MTCs effectively inhibited the pharmacologically relevant human (h) hCAs isoforms I, II, IX, and XII in vitro and showed KIs spanning between the low and medium nanomolar range. By means of a computational study, the MTC moiety binding mode on the CAs was explained. Furthermore, a selection of MTCs were evaluated in a normotensive glaucoma rabbit model for their intraocular pressure (IOP) lowering effects and showed interesting activity.