Carbonic anhydrase inhibitors. Inhibition of cytosolic isoforms I, II, III, VII and XIII with less investigated inorganic anions.
An inhibition study of the cytosolic carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, III, VII and XIII with anions such as stannate(IV), selenate(VI), tellurate(VI), perosmate(VIII), persulfate, pyrophosphate(V), pyrovanadate(V), tetraborate, persulfate, perrhenate(VII), perrutenate(VII), selenocyanate, iminodisulfonate, fluorosulfate and trithiocarbonate is reported. Trithiocarbonate was the best inhibitor detected, showing affinities of 8.7-9.9 microM for CA I-III, of 36.15 mM for CA VII and of 0.43 mM for CA XIII. Considering trithiocarbonate as lead, we show that compounds incorporating the new zinc-binding group CS2-, such as among other the dithiocarbamates, are even more active inhibitors, with submicromolar inhibitory activity. New classes of CA inhibitors are being detected based on the CS2- zinc-binding group.
Innocenti
Alessio
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Firenze, Italy.
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000838:Anions / Q000737:chemistry*; D024401:Carbonic Anhydrase I / Q000737:chemistry / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000737:chemistry / Q000378:metabolism; D024403:Carbonic Anhydrase III / Q000737:chemistry / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000737:chemistry*; D002256:Carbonic Anhydrases / Q000737:chemistry* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry; D005028:Ethylenebis(dithiocarbamates) / Q000737:chemistry; D006801:Humans; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D013871:Thiones / Q000737:chemistry; D015032:Zinc / Q000737:chemistry
D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D002352:Carrier Proteins; D005028:Ethylenebis(dithiocarbamates); D020033:Protein Isoforms; D013871:Thiones; C017800:zinc-binding protein; D024401:Carbonic Anhydrase I; D024402:Carbonic Anhydrase II; D024403:Carbonic Anhydrase III; C483903:CA13 protein, human; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI; D015032:Zinc; C013321:trithiocarbonic acid