Chinchilli Krishna Kartheek, Angeli Andrea, Thacker Pavitra S, Korra Laxman Naik, Biswas Rashmita, Arifuddin Mohammed, Supuran Claudiu T
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Balanagar, Hyderabad 500037, India.
Neurofarba Department, Sezione di Scienze Farmaceutiche e Nutraceutiche, Università degli Studi di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Metabolites. 2020 May 15;10(5):200. doi: 10.3390/metabo10050200.
A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (6a-6o) was synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against the human (h) isoforms hCA I, II, XIII (cytosolic isoforms), and hCA IX (transmembrane tumor-associated isoform). The results revealed that the compounds exhibited K values in the low to medium nanomolar range against hCA II and hCA IX (Ks ranging from 7.7 nM to 41.3 nM) and higher K values against hCA I and hCA XIII. Compound showed potent inhibition of hCA II (K = 7.7nM), being more effective compared to the standard inhibitor acetazolamide (AAZ) (K = 12.1 nM). Compounds and showed moderate activity against hCA XIII (K= 69.8 and 65.8 nM). Hence, compound could be consider as potential lead candidate for the design of potent and selective hCA II inhibitors.
合成了一系列1,2,3-三唑连接的三嗪并[5,6-b]吲哚-苯磺酰胺杂合物（6a - 6o），并评估了它们对人（h）同工型hCA I、II、XIII（胞质同工型）和hCA IX（跨膜肿瘤相关同工型）的碳酸酐酶（CA，EC 4.2.1.1）抑制活性。结果表明，这些化合物对hCA II和hCA IX的K值在低至中纳摩尔范围内（K值范围为7.7 nM至41.3 nM），而对hCA I和hCA XIII的K值更高。化合物对hCA II表现出强效抑制作用（K = 7.7 nM），与标准抑制剂乙酰唑胺（AAZ）（K = 12.1 nM）相比更有效。化合物和对hCA XIII表现出中等活性（K = 69.8和65.8 nM）。因此，化合物可被视为设计强效和选择性hCA II抑制剂的潜在先导候选物。
