Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition
Simone Giovannuzzi1, Andrea Angeli1, Paloma Begines1,2
1NEUROFARBA Department, Section of Pharmaceutical Science, University of Florence, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
Abstract:
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 K I 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.
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