Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition
The tetrazole group is here proposed as a zinc-binding warhead for the inhibition of the metalloenzyme carbonic anhydrases. A set of synthesized derivatives incorporating the tetrazole moiety were evaluated as inhibitors against a panel of human isoforms, exhibiting <i>K</i> <sub>I</sub> values spanning between the submicromolar and low-to-medium micromolar ranges (0.62-19.6 μM). X-ray crystallographic studies were conducted to gain insights into their modes of binding to the target enzyme. These findings mark a significant advancement in the search for inhibitory chemotypes other than classical sulfonamides.
Authors
- Simone Giovannuzzi (ORCID: https://orcid.org/0000-0002-0669-7481)
- Paloma Begines (ORCID: https://orcid.org/0000-0001-5188-2005)
- Alessio Nocentini (ORCID: https://orcid.org/0000-0003-3342-702X)
- Marta Ferraroni (ORCID: https://orcid.org/0000-0001-7258-738X)
- Claudiu T. Supuran (ORCID: https://orcid.org/0000-0003-4262-0323)
- Andrea Angeli (ORCID: https://orcid.org/0000-0002-1470-7192)
Institutions
- Institute of Organic Chemistry (HU)
- University of Florence (IT)
- Universidad de Sevilla (ES)
Publication Details
- Journal
- ACS Medicinal Chemistry Letters
- Published
- 2024-12-25
- DOI
- https://doi.org/10.1021/acsmedchemlett.4c00562
- Citations
- 4
- Primary Topic
- Enzyme function and inhibition
- Type
- article
- Field-Weighted Citation Impact
- 0.94