New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators

A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length o...

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Autores principales: Chiaramonte, Niccolò, Gabellini, Alessio, Angeli, Andrea, Bartolucci, Gianluca, Braconi, Laura, Dei, Silvia, Teodori, Elisabetta, Supuran, Claudiu T., Romanelli, Maria Novella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779960/
https://www.ncbi.nlm.nih.gov/pubmed/35056859
http://dx.doi.org/10.3390/molecules27020545
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author Chiaramonte, Niccolò
Gabellini, Alessio
Angeli, Andrea
Bartolucci, Gianluca
Braconi, Laura
Dei, Silvia
Teodori, Elisabetta
Supuran, Claudiu T.
Romanelli, Maria Novella
author_facet Chiaramonte, Niccolò
Gabellini, Alessio
Angeli, Andrea
Bartolucci, Gianluca
Braconi, Laura
Dei, Silvia
Teodori, Elisabetta
Supuran, Claudiu T.
Romanelli, Maria Novella
author_sort Chiaramonte, Niccolò
collection PubMed
description A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (K(A) values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.
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spelling pubmed-87799602022-01-22 New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators Chiaramonte, Niccolò Gabellini, Alessio Angeli, Andrea Bartolucci, Gianluca Braconi, Laura Dei, Silvia Teodori, Elisabetta Supuran, Claudiu T. Romanelli, Maria Novella Molecules Article A series of histamine (HST)-related compounds were synthesized and tested for their activating properties on five physiologically relevant human Carbonic Anhydrase (hCA) isoforms (I, II, Va, VII and XIII). The imidazole ring of HST was replaced with different 5-membered heterocycles and the length of the aliphatic chain was varied. For the most interesting compounds some modifications on the terminal amino group were also performed. The most sensitive isoform to activation was hCA I (K(A) values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives (1, 3a and 22) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII. MDPI 2022-01-15 /pmc/articles/PMC8779960/ /pubmed/35056859 http://dx.doi.org/10.3390/molecules27020545 Text en © 2022 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
Chiaramonte, Niccolò
Gabellini, Alessio
Angeli, Andrea
Bartolucci, Gianluca
Braconi, Laura
Dei, Silvia
Teodori, Elisabetta
Supuran, Claudiu T.
Romanelli, Maria Novella
New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title_full New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title_fullStr New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title_full_unstemmed New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title_short New Histamine-Related Five-Membered N-Heterocycle Derivatives as Carbonic Anhydrase I Activators
title_sort new histamine-related five-membered n-heterocycle derivatives as carbonic anhydrase i activators
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779960/
https://www.ncbi.nlm.nih.gov/pubmed/35056859
http://dx.doi.org/10.3390/molecules27020545
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