Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates

Acetylated triterpenoids betulin, oleanolic acid, ursolic acid, and glycyrrhetinic acid were converted into their succinyl-spacered acetazolamide conjugates. These conjugates were screened for their inhibitory activity onto carbonic anhydrase II and their cytotoxicity employing several human tumor c...

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Autores principales: Denner, Toni C., Heise, Niels, Zacharias, Julian, Kraft, Oliver, Hoenke, Sophie, Csuk, René
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919727/
https://www.ncbi.nlm.nih.gov/pubmed/36770674
http://dx.doi.org/10.3390/molecules28031009
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author Denner, Toni C.
Heise, Niels
Zacharias, Julian
Kraft, Oliver
Hoenke, Sophie
Csuk, René
author_facet Denner, Toni C.
Heise, Niels
Zacharias, Julian
Kraft, Oliver
Hoenke, Sophie
Csuk, René
author_sort Denner, Toni C.
collection PubMed
description Acetylated triterpenoids betulin, oleanolic acid, ursolic acid, and glycyrrhetinic acid were converted into their succinyl-spacered acetazolamide conjugates. These conjugates were screened for their inhibitory activity onto carbonic anhydrase II and their cytotoxicity employing several human tumor cell lines and non-malignant fibroblasts. As a result, the best inhibitors were derived from betulin and glycyrrhetinic acid while those derived from ursolic or oleanolic acid were significantly weaker inhibitors but also of diminished cytotoxicity. A betulin-derived conjugate held a K(i) = 0.129 μM and an EC(50) = 8.5 μM for human A375 melanoma cells.
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spelling pubmed-99197272023-02-12 Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates Denner, Toni C. Heise, Niels Zacharias, Julian Kraft, Oliver Hoenke, Sophie Csuk, René Molecules Article Acetylated triterpenoids betulin, oleanolic acid, ursolic acid, and glycyrrhetinic acid were converted into their succinyl-spacered acetazolamide conjugates. These conjugates were screened for their inhibitory activity onto carbonic anhydrase II and their cytotoxicity employing several human tumor cell lines and non-malignant fibroblasts. As a result, the best inhibitors were derived from betulin and glycyrrhetinic acid while those derived from ursolic or oleanolic acid were significantly weaker inhibitors but also of diminished cytotoxicity. A betulin-derived conjugate held a K(i) = 0.129 μM and an EC(50) = 8.5 μM for human A375 melanoma cells. MDPI 2023-01-19 /pmc/articles/PMC9919727/ /pubmed/36770674 http://dx.doi.org/10.3390/molecules28031009 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Denner, Toni C.
Heise, Niels
Zacharias, Julian
Kraft, Oliver
Hoenke, Sophie
Csuk, René
Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title_full Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title_fullStr Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title_full_unstemmed Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title_short Small Structural Differences Govern the Carbonic Anhydrase II Inhibition Activity of Cytotoxic Triterpene Acetazolamide Conjugates
title_sort small structural differences govern the carbonic anhydrase ii inhibition activity of cytotoxic triterpene acetazolamide conjugates
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9919727/
https://www.ncbi.nlm.nih.gov/pubmed/36770674
http://dx.doi.org/10.3390/molecules28031009
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