A series of new, halogen containing N-substituted 4-aminobenzenesulfonamides were synthesized by using superacid HF/SbF(5) 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 β position of the sulfonamide function strongly favors hCA inhibition. A similar effect of the β-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.
Superacid synthesis of halogen containing N-substituted-4-aminobenzene sulfonamides: New selective tumor-associated carbonic anhydrase inhibitors / G. Compain;A. Martin-Mingot;A. Maresca;S. Thibaudeau;C. T. Supuran. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 21:(2013), pp. 1555-1563. [10.1016/j.bmc.2012.05.037]
Superacid synthesis of halogen containing N-substituted-4-aminobenzene sulfonamides: New selective tumor-associated carbonic anhydrase inhibitors.
SUPURAN, CLAUDIU TRANDAFIR
2013
Abstract
A series of new, halogen containing N-substituted 4-aminobenzenesulfonamides were synthesized by using superacid HF/SbF(5) 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 β position of the sulfonamide function strongly favors hCA inhibition. A similar effect of the β-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.I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.