Monothiocarbamates Strongly Inhibit Carbonic Anhydrases in Vitro and Possess Intraocular Pressure Lowering Activity in an Animal Model of Glaucoma

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.