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4-Substituted Pyridine-3-Sulfonamides as Carbonic Anhydrase Inhibitors Modified by Click Tailing: Synthesis, Activity, and Docking Studies
Abstract
In the search for new selective inhibitors of human carbonic anhydrase (hCA), particularly the cancer-associated isoforms hCA IX and hCA XII, a series of 4-substituted pyridine-3-sulfonamides was synthesized using the “click” CuAAC reaction, proven by X-ray crystallography, and evaluated for their inhibitory activity against hCA I, hCA II, hCA IX, and hCA XII. Additional molecular docking studies and cytostatic activity assays on three cancer cell lines were conducted. The compounds exhibited a broad range of inhibitory activity, with KI reaching 271 nM for hCA II, 137 nM for hCA IX, and 91 nM for hCA XII. Notably, compound 4 demonstrated up to 5.9-fold selectivity toward the cancerassociated hCA IX over the ubiquitous hCA II, while compound 6 exhibited a remarkable 23.3-fold selectivity between transmembrane isoforms hCA IX and hCA XII. Molecular docking studies have shown the possibility of selective interaction with the hydrophilic or lipophilic half of the active site, what results from the adjacent (3,4) position of the “tail” in relation to the sulfonamide group.
Citations
Authors (7)
-
Krzysztof Szafrański dr
- Medical University of Gdańsk
-
Jarosław Sławiński
- Medical University of Gdańsk
-
Anna Kawiak
- Intercollegiate Faculty of Biotechnology, University of Gdańsk
-
Michał Kosno
- Medical University od Gdańsk
-
Andrea Ammara
- Universit`a degli Studi di Firenze, Italy
-
Claudiu T. Supuran
- Universit`a degli Studi di Firenze, Italy
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- Category:
- Articles
- Type:
- artykuły w czasopismach
- Published in:
-
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
no. 26,
ISSN: 1661-6596 - Language:
- English
- Publication year:
- 2025
- Bibliographic description:
- Szafrański K., Sławiński J., Kawiak A., Chojnacki J., Kosno M., Ammara A., Supuran C. T.: 4-Substituted Pyridine-3-Sulfonamides as Carbonic Anhydrase Inhibitors Modified by Click Tailing: Synthesis, Activity, and Docking Studies// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 26,iss. 8 (2025), s.3817-
- DOI:
- Digital Object Identifier (open in new tab) 10.3390/ijms26083817
- Sources of funding:
-
- Free publication
- Verified by:
- Gdańsk University of Technology
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