Design and synthesis of benzenesulfonamide-linked imidazo[2,1-b][1,3,4]thiadiazole derivatives as carbonic anhydrase I and II inhibitors
| Autor: | Venkata M. Yaddanapudi, Claudiu T. Supuran, Abhay Kothari, Andrea Angeli, Kamtam Aashritha, Mohammed Arifuddin, Dilep Kumar Sigalapalli, Priti Singh, Baijayantimala Swain |
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| Rok vydání: | 2021 |
| Předmět: |
Gene isoform
Carbonic Anhydrase I Stereochemistry Pharmaceutical Science DABCO 01 natural sciences Carbonic Anhydrase II chemistry.chemical_compound Structure-Activity Relationship Carbonic anhydrase Drug Discovery Thiadiazoles Humans Carbonic Anhydrases chemistry.chemical_classification Sulfonamides biology 010405 organic chemistry Imidazoles 0104 chemical sciences Sulfonamide Molecular Docking Simulation 010404 medicinal & biomolecular chemistry Cytosol Enzyme chemistry 1 3 4 thiadiazole derivatives biology.protein |
| Zdroj: | Archiv der PharmazieREFERENCES. 354(7) |
| ISSN: | 1521-4184 |
| Popis: | A novel series of imidazothiadiazole-linked benzenesulfonamide derivatives (5a-t) was synthesized and subjected for screening against the four physiologically and pharmacologically relevant human carbonic anhydrase (hCA) isoforms: hCA I, II, VA, and IX. The compounds selectively inhibited hCA I and II over hCA VA and IX. Furthermore, among the two cytosolic isoforms, hCA II was more effectively inhibited as compared with hCA I. The most active compounds were 5o with K i = 0.246 µM and 5p with K i = 0.376 µM against hCA II, whereas compound 5f showed good inhibition against both hCA I and II with K i = 0.493 and 0.4 µM, respectively. This class of underexplored sulfonamides may be used to design isoform-selective CA inhibitors targeting enzymes of medicinal chemistry interest. |
| Databáze: | OpenAIRE |
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