Superacid synthesis of halogen containing N-substituted-4-aminobenzene sulfonamides: new selective tumor-associated carbonic anhydrase inhibitors.

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Compain G, Martin-Mingot A, Maresca A, Thibaudeau S, Supuran CT

Superacid synthesis of halogen containing N-substituted-4-aminobenzene sulfonamides: new selective tumor-associated carbonic anhydrase inhibitors.

Bioorg Med Chem. 2013 Mar 15;21(6):1555-63. doi: 10.1016/j.bmc.2012.05.037. Epub 2012 May 26.

PubMed ID

22705188 [ View in PubMed

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Abstract

A series of new, halogen containing N-substituted 4-aminobenzenesulfonamides were synthesized by using superacid HF/SbF5 chemistry and investigated as inhibitors of several human carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, that is, the cytosolic hCA I and II and, the tumor-associated transmembrane isoforms hCA IX and XII. Despite the substitution of the sulfonamide function, the presence of fluorine atom(s) in beta position of the sulfonamide function strongly favors hCA inhibition. A similar effect of the beta-fluorinated alkyl substitution on the amino function has been also observed. Among the tested compounds, several chlorinated derivatives have been identified as selective nanomolar, tumor-associated isoforms inhibitors. These non-primary sulfonamides probably bind in the coumarin-binding site, at the entrance of the cavity, and not to the metal ion as the primary sulfonamide inhibitors.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-({[4-(AMINOSULFONYL)PHENYL]AMINO}CARBONYL)-4-METHYLBENZENESULFONAMIDE	Carbonic anhydrase 2	Ki (nM)	12	N/A	N/A	Details