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. 2020 Jun;99:103839. doi: 10.1016/j.bioorg.2020.103839. Epub 2020 Apr 8.
Sulfonamide is one of the most promising classes of classical carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. A novel series of indolylchalcones incorporating benzenesulfonamide-1,2,3-triazole (6a-q) has been synthesized by click chemistry reaction and investigated for hCA inhibitory activity against a panel of human carbonic anhydrases (hCAs). Most of these newly synthesized compounds exhibited interesting inhibition constants, in the nanomolar range, with some derivatives being more potent than the standard drug acetazolamide (AAZ) on hCA I isoform. Among the tested compounds, the compounds 6d (18.8 nM), 6q (38.3 nM) and 6e (50.4 nM) were 13, 6 and 5 times more potent than AAZ against hCA I isoform, respectively. Compounds 6o, 6m and 6f efficiently inhibited isoform hCA XII, with Ks in the range of 10-41.9 nM. Several compounds were also active against isoforms hCA II and hCA IX, with Ks under 100 nM. These indolylchalcone-benzenesulfonamide-1,2,3-triazole hybrids may be considered as potential leads for hCA I-selective inhibitors.
磺胺类药物是最有前途的经典碳酸酐酶 (CA, EC 4.2.1.1) 抑制剂之一。通过点击化学反应合成了一系列新型吲哚查尔酮，其中包含苯磺酰胺-1,2,3-三唑 (6a-q)，并对其进行了对一组人碳酸酐酶 (hCA) 的抑制活性研究。这些新合成的化合物大多数表现出有趣的抑制常数，在纳摩尔范围内，一些衍生物对 hCA I 同工型的抑制活性比标准药物乙酰唑胺 (AAZ) 更强。在所测试的化合物中，化合物 6d (18.8 nM)、6q (38.3 nM) 和 6e (50.4 nM) 对 hCA I 同工型的抑制活性分别比 AAZ 强 13、6 和 5 倍。化合物 6o、6m 和 6f 对 hCA XII 同工型有效抑制，Ks 值在 10-41.9 nM 范围内。一些化合物对 hCA II 和 hCA IX 同工型也具有活性，Ks 值低于 100 nM。这些吲哚查尔酮-苯磺酰胺-1,2,3-三唑杂合体可以被认为是 hCA I 选择性抑制剂的潜在先导化合物。
