Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India.
UniversitàdegliStudi di Firenze, Neurofarba Dept, Sezione di ScienzeFarmaceutiche e, Nutraceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Bioorg Chem. 2021 Mar;108:104647. doi: 10.1016/j.bioorg.2021.104647. Epub 2021 Jan 19.
The primary sulfonamide group is one of the most efficient zinc binding group (ZBG) for designing carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. In the present study primary sulfonamide linked with indolylchalcone were designed. The newly synthesized molecules (5a-r) were examined against four human (h) CA isoforms (hCA I, hCA II, hCA IX and hCA XIII). These sulfonamides showed good inhibition activity against isoforms hCA I, hCA II and hCA XIII. Compound 5i (2.3 nM), 5m (2.4 nM), 5o (3.6 nM) and 5q (7.0 nM) were more potent than standard drug AAZ (12.1 nM) against isoform hCA II, respectively. Most of the other compounds in the present series inhibited hCA XIII and hCA IX in the range of 50 nM - 100 nM.
磺胺基是设计碳酸酐酶（CA，EC 4.2.1.1）抑制剂最有效的锌结合基团（ZBG）之一。在本研究中，设计了与吲哚查尔酮相连的初级磺胺基。新合成的分子（5a-r）针对四种人（h）CA 同工酶（hCA I、hCA II、hCA IX 和 hCA XIII）进行了测试。这些磺胺类化合物对 hCA I、hCA II 和 hCA XIII 同工酶表现出良好的抑制活性。化合物 5i（2.3 nM）、5m（2.4 nM）、5o（3.6 nM）和 5q（7.0 nM）对 hCA II 同工酶的抑制活性强于标准药物 AAZ（12.1 nM）。本系列中的大多数其他化合物对 hCA XIII 和 hCA IX 的抑制作用在 50 nM-100 nM 范围内。
