advertisement
Abstract #48967 Published in IGR 14-1
Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo
Carta F; Aggarwal M; Maresca A; Scozzafava A; McKenna R; Masini E; Supuran CTJournal of Medicinal Chemistry 2012; 55: 1721-1730
A series of dithiocarbamates were prepared by reaction of primary/secondary amines with carbon disulfide in the presence of bases. These compounds were tested for the inhibition of four human (h) isoforms of the zinc enzyme carbonic anhydrase, CA (EC 4.2.1.1), hCA I, II, IX, and XII, involved in pathologies such as glaucoma (CA II and XII) or cancer (CA IX). Several low nanomolar inhibitors targeting these CAs were detected. The X-ray crystal structure of the hCA II adduct with morpholine dithiocarbamate evidenced the inhibition mechanism of these compounds, which coordinate to the metal ion through a sulfur atom from the dithiocarbamate zinc-binding function. Some dithiocarbamates showed an effective intraocular pressure lowering activity in an animal model of glucoma.
Laboratorio di Chimica Bioinorganica, Polo Scientifico, Università degli Studi di Firenze, Room 188, Via della Lastruccia 3, 50019 Sesto Fiorentino, Florence, Italy.
Full articleClassification:
11.14 Investigational drugs; pharmacological experiments (Part of: 11 Medical treatment)
11.5 Carbonic anhydrase inhibitors (Part of: 11 Medical treatment)