Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1377331 | Bioorganic & Medicinal Chemistry Letters | 2008 | 7 Pages |
Abstract
2-N,N-Dimethylamino-1,3,4-thiadiazole-5-methanesulfonamide was tested for its interaction with the 12 catalytically active mammalian carbonic anhydrase (CA, EC 4.2.1.1) isozymes, CA I-XIV. The compound is a potent inhibitor of CA IV, VII, IX, XII, and XIII (KIs of 0.61-39Â nM), a medium potency inhibitor of CA II and VA (KIs of 121-438Â nM), and a weak inhibitor against the other isoforms (CA III, VB, VI, and XIV), making it a very interesting candidate for situations in which a strong/selective inhibition of certain isozymes is needed. The crystal structure of the hCA II adduct of this sulfonamide revealed interesting interactions between the inhibitor and the enzyme which are quite different from those observed in the adducts of CA II with the structurally related aliphatic derivatives zonisamide, 2-amino-1,3,4-thiadiazolyl-5-difluoromethanesulfonamide, and 2-dimethylamino-5-[sulfonamido-(aminomethyl)]-1,3,4-thiadiazole reported earlier.
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Authors
Claudia Temperini, Alessandro Cecchi, Nicholas A. Boyle, Andrea Scozzafava, Jaime Escribano Cabeza, Paul Jr., G. Michael Blackburn, Claudiu T. Supuran,