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
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Egyptian Russian University, Badr City, Cairo, P.O. Box 11829, Egypt.
Eur J Med Chem. 2016 Mar 3;110:259-66. doi: 10.1016/j.ejmech.2016.01.030. Epub 2016 Jan 20.
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 KIs in the range of 7.9-894 nM, hCA II in the range of 7.5-1645 nM (with one compound having a KI > 10 μM); 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.
通过分子杂交方法，合成了两个系列含有取代异吲哚酮部分的酰胺基/脲基取代苯磺酰胺。对所制备的衍生物进行体外评估，考察其对人碳酸酐酶（hCA，EC 4.2.1.1）I、II（胞质型）以及IX、XII（跨膜型、肿瘤相关型）同工酶的抑制活性。本文报道的磺酰胺对所有这些同工酶均有不同程度的抑制作用。hCA I的抑制常数（KI）在7.9 - 894 nM范围内，hCA II的KI在7.5 - 1645 nM范围内（有一种化合物的KI > 10 μM）；hCA IX的KI在5.0 - 240 nM范围内，而hCA XII的KI在0.47 - 2.83 nM范围内。由于所有这些同工酶都参与多种病理过程，对它们的抑制可用于治疗，本文报道的衍生物可能代表磺酰胺类碳酸酐酶抑制剂领域有趣的拓展。
