178606-64-9Relevant academic research and scientific papers
Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis
Pacchiano, Fabio,Carta, Fabrizio,McDonald, Paul C.,Lou, Yuanmei,Vullo, Daniela,Scozzafava, Andrea,Dedhar, Shoukat,Supuran, Claudiu T.
supporting information; experimental part, p. 1896 - 1902 (2011/05/17)
A series of ureido-substituted benzenesulfonamides was prepared that showed a very interesting profile for the inhibition of several human carbonic anhydrases (hCAs, EC 4.2.1.1), such as hCAs I and II (cytosolic isoforms) and hCAs IX and XII (transmembrane, tumor-associated enzymes). Excellent inhibition of all these isoforms has been observed with various members of the series, depending on the substitution pattern of the urea moiety. Several low nanomolar CA IX/XII inhibitors also showing good selectivity for the transmembrane over the cytosolic isoforms have been discovered. One of them, 4-{[(3′- nirophenyl)carbamoyl]amino}benzenesulfonamide, significantly inhibited the formation of metastases by the highly aggressive 4T1 mammary tumor cells at pharmacologic concentrations of 45 mg/kg, constituting an interesting candidate for the development of conceptually novel antimetastatic drugs.
Inhibition of β-carbonic anhydrases with ureido-substituted benzenesulfonamides
Pacchiano, Fabio,Carta, Fabrizio,Vullo, Daniela,Scozzafava, Andrea,Supuran, Claudiu T.
experimental part, p. 102 - 105 (2011/02/25)
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 β-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 Kis 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 α- and β-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.
