Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo.

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Carta F, Aggarwal M, Maresca A, Scozzafava A, McKenna R, Masini E, Supuran CT

Dithiocarbamates strongly inhibit carbonic anhydrases and show antiglaucoma action in vivo.

J Med Chem. 2012 Feb 23;55(4):1721-30. doi: 10.1021/jm300031j. Epub 2012 Feb 13.

PubMed ID

22276570 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 12	Ki (nM)	5.7	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details