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 KI 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.
Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition / Giovannuzzi S.; Angeli A.; Begines P.; Ferraroni M.; Nocentini A.; Supuran C.T.. - In: ACS MEDICINAL CHEMISTRY LETTERS. - ISSN 1948-5875. - ELETTRONICO. - 16:(2025), pp. 163-166. [10.1021/acsmedchemlett.4c00562]
Tetrazole Is a Novel Zinc Binder Chemotype for Carbonic Anhydrase Inhibition
Giovannuzzi S.;Angeli A.;Ferraroni M.;Nocentini A.;Supuran C. T.
2025
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 KI 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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