1,2,3-三唑连接的三嗪并[5,6-b]吲哚-苯磺酰胺缀合物作为强效碳酸酐酶I、II、IX和XIII抑制剂的设计、合成及生物学评价
Design, Synthesis, and Biological Evaluation of 1,2,3-Triazole-Linked Triazino[5,6-B]Indole-Benzene Sulfonamide Conjugates as Potent Carbonic Anhydrase I, II, IX, and XIII Inhibitors.
作者信息
Chinchilli Krishna Kartheek, Angeli Andrea, Thacker Pavitra S, Korra Laxman Naik, Biswas Rashmita, Arifuddin Mohammed, Supuran Claudiu T
机构信息
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.
出版信息
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。
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