Potent isothiocyanate inhibitors of carbonic anhydrase: synthesis and evaluation.
The reversible hydration of carbon dioxide by carbonic anhydrase (CA) regulates pH and carbon dioxide concentrations in diverse biological systems. Potent irreversible inhibition of CA would facilitate study of the dynamics of CA turnover as well as therapeutic effects due to long-term inhibition of the enzyme. We have synthesized isothiocyanate-containing sulfonamide inhibitors of CA from the corresponding aminosulfonamides. Significant increases in apparent binding of some of the isothiocyanate inhibitors over the amine analogues were consistent with covalent inhibition of the enzyme.
Khobzaoui
Moussa
M
Department of Chemistry, College of Arts and Sciences, University of Toledo, Toledo, OH 43606, USA.
Tillekeratne
L M Viranga
LM
Hudson
Richard A
RA
D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D005069:Evaluation Studies as Topic; D020128:Inhibitory Concentration 50; D017879:Isothiocyanates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry
D002257:Carbonic Anhydrase Inhibitors; D017879:Isothiocyanates; D013449:Sulfonamides; D002256:Carbonic Anhydrases