Amido/ureidosubstituted benzenesulfonamides-isatin conjugates as low nanomolar/subnanomolar inhibitors of the tumor-associated carbonic anhydrase isoform XII

作者：Eldehna Wagdy M^*; Fares Mohamed; Ceruso Mariangela; Ghabbour Hazem A; Abou Seri Sahar M; Abdel Aziz Hatem A; Abou El Ella Dalal A; Supuran Claudiu T^*

来源：European Journal of Medicinal Chemistry, 2016, 110: 259-266.

DOI：10.1016/j.ejmech.2016.01.030

• Carbonic anhydrase
• Tumor-associated isoforms
• Amido/ureido sulfonamides
• Isatin

By using a molecular hybridization approach, two series of amido/ureidosubstituted benzenesulfonamides incorporating substituted-isatin moieties were synthesized. The prepared derivatives were in vitro evaluated for their inhibitory activity against human carbonic anhydrase (hCA, EC 4.2.1.1) I, II (cytosolic) and IX, XII (transmembrane, tumor-associated) isoforms. All these isoforms were inhibited in variable degrees by the sulfonamides reported here. hCA I was inhibited with K(I)s in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a K-I > 10 mu M); hCA IX in the range of 5.0-240 nM, whereas hCA XII in the range of 0.47-2.83 nM. As all these isoforms are involved in various pathologies, in which their inhibition can be exploited therapeutically, the derivatives reported here may represent interesting extensions to the field of CA inhibitors of the sulfonamide type.

• 出版日期2016-3-3