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
oleh: Krishna Kartheek Chinchilli, Andrea Angeli, Pavitra S. Thacker, Laxman Naik Korra, Rashmita Biswas, Mohammed Arifuddin, Claudiu T. Supuran
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2020-05-01 |
Deskripsi
A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (<b>6a–6o</b>) 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 <b>6a–6o</b> exhibited K<sub>i</sub> values in the low to medium nanomolar range against hCA II and hCA IX (K<sub>i</sub>s ranging from 7.7 nM to 41.3 nM) and higher K<sub>i</sub> values against hCA I and hCA XIII. Compound <b>6i</b> showed potent inhibition of hCA II (K<sub>i</sub> = 7.7nM), being more effective compared to the standard inhibitor acetazolamide (AAZ) (K<sub>i</sub> = 12.1 nM). Compounds <b>6b</b> and <b>6d</b> showed moderate activity against hCA XIII (K<sub>i</sub> = 69.8 and 65.8 nM). Hence, compound <b>6i</b> could be consider as potential lead candidate for the design of potent and selective hCA II inhibitors.