Department of Chemical Sciences National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad, 500037, India.
Università degli Studi di Firenze, Neurofarba Dept., Sezione di Scienze Farmaceutiche e Nutraceutiche, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Florence, Italy.
Eur J Med Chem. 2022 Apr 15;234:114247. doi: 10.1016/j.ejmech.2022.114247. Epub 2022 Mar 9.
A novel series of 32 sulfonamide containing quinolines (5a-j, 7a-k and 9a-k) were synthesized using tail approach and assayed for their carbonic anhydrase inhibitory potency against four human (h) carbonic anhydrase (CA) isoforms hCA I, II, IX and XII. Most of these newly synthesized compounds exhibited interesting inhibition potency against hCA I, II, IX and XII, in the nanomolar range with some derivatives being more potent than the standard drug acetazolamide (AAZ). The most effective ones on hCA I were 9b (91.8 nM), on hCA II: 5b (7.1 nM), 9c (9.6 nM) and on hCA IX: 5b (6.5 nM), 5g (21.4 nM), 5i (9.1 nM), 9a (22.8 nM), 9b (9.7 nM). Compounds 5h (8.8 nM), 7a (9.6 nM), 9d (6.9 nM), 9e (6.7 nM) were found highly effective against hCA XII. These 4-functionalized benzenesulfonamides (5a-5j, 9a-9k) were found to be more potent than the corresponding 3-functionalized derivatives (7a-k). These compounds may emerge as potential leads for the development of isoform selective hCA IX and XII inhibitors.
合成了一系列 32 个含有磺胺的喹啉（5a-j、7a-k 和 9a-k），采用尾进法进行合成，并对它们抑制四种人源碳酸酐酶（hCA）同工酶 hCA I、II、IX 和 XII 的活性进行了测试。这些新合成的化合物大多数对 hCA I、II、IX 和 XII 具有有趣的抑制活性，其抑制活性在纳摩尔范围内，一些衍生物比标准药物乙酰唑胺（AAZ）更有效。对 hCA I 最有效的化合物是 9b（91.8 nM），对 hCA II 最有效的化合物是 5b（7.1 nM）、9c（9.6 nM），对 hCA IX 最有效的化合物是 5b（6.5 nM）、5g（21.4 nM）、5i（9.1 nM）、9a（22.8 nM）、9b（9.7 nM）。对 hCA XII 最有效的化合物是 5h（8.8 nM）、7a（9.6 nM）、9d（6.9 nM）、9e（6.7 nM）。这些 4-取代苯磺酰胺（5a-5j、9a-9k）比相应的 3-取代衍生物（7a-k）更有效。这些化合物可能成为开发同工酶选择性 hCA IX 和 XII 抑制剂的潜在先导化合物。
