Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis.

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Pacchiano F, Carta F, McDonald PC, Lou Y, Vullo D, Scozzafava A, Dedhar S, Supuran CT

Ureido-substituted benzenesulfonamides potently inhibit carbonic anhydrase IX and show antimetastatic activity in a model of breast cancer metastasis.

J Med Chem. 2011 Mar 24;54(6):1896-902. doi: 10.1021/jm101541x. Epub 2011 Mar 1.

PubMed ID

21361354 [ View in PubMed

]

Abstract

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'-nitrophenyl)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.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Acetazolamide	Carbonic anhydrase 1	Ki (nM)	250	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 12	Ki (nM)	5.7	N/A	N/A	Details
Acetazolamide	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details