Inhibition of beta-carbonic anhydrases with ureido-substituted benzenesulfonamides.

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Pacchiano F, Carta F, Vullo D, Scozzafava A, Supuran CT

Inhibition of beta-carbonic anhydrases with ureido-substituted benzenesulfonamides.

Bioorg Med Chem Lett. 2011 Jan 1;21(1):102-5. doi: 10.1016/j.bmcl.2010.11.064. Epub 2010 Nov 20.

PubMed ID

21145236 [ View in PubMed

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Abstract

A series of sulfonamides was prepared by reaction of sulfanilamide with aryl/alkyl isocyanates. The ureido-substituted benzenesulfonamides showed a very interesting profile for the inhibition of several carbonic anhydrases (CAs, EC 4.2.1.1) such as the human hCA II and three beta-CAs from pathogenic fungal or bacterial species. The Candida albicans enzyme was inhibited with potencies in the range of 3.4-3970 nM, whereas the Mycobacterium tuberculosis enzymes Rv1284 and Rv3273 were inhibited with K(i)s in the range of 4.8-6500 nM and of 6.4-6850 nM, respectively. The structure-activity relationship for this class of inhibitors is rather complex, but the main features associated with effective inhibition of both alpha- and beta-CAs investigated here have been delineated. The nature of the moiety substituting the second ureido nitrogen is the determining factor in controlling the inhibitory power, probably due to the flexibility of the ureido linker and the possibility of this moiety to orientate in different subpockets of the active site cavities of these enzymes.

DrugBank Data that Cites this Article

Binding Properties

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