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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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2022-01, Vol.27 (2), p.545
Main Authors: Chiaramonte, Niccolò, Gabellini, Alessio, Angeli, Andrea, Bartolucci, Gianluca, Braconi, Laura, Dei, Silvia, Teodori, Elisabetta, Supuran, Claudiu T, Romanelli, Maria Novella
Format: Article
Language:English
Subjects:
Amino acids
Carbon dioxide
Carbonic anhydrase
carbonic anhydrase activators
Carbonic Anhydrase I - drug effects
Carbonic Anhydrase I - metabolism
Carbonic Anhydrase II - drug effects
Carbonic Anhydrase II - metabolism
Carbonic Anhydrase V - drug effects
Carbonic Anhydrase V - metabolism
Carbonic Anhydrases - drug effects
Carbonic Anhydrases - metabolism
Enzymes
heterocycles
Heterocyclic Compounds, 4 or More Rings - chemical synthesis
Heterocyclic Compounds, 4 or More Rings - chemistry
Heterocyclic Compounds, 4 or More Rings - pharmacology
Histamine
Histamine - analogs & derivatives
Histamine - chemical synthesis
Histamine - chemistry
Histamine - pharmacology
histamine-related compounds
Humans
Hydration
Hydrogen bonds
Hypotheses
Imidazole
Imidazoles - chemistry
Protein Isoforms - drug effects
Protein Isoforms - metabolism
Selectivity
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Summary: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 values in the low micromolar range), but surprisingly none of the new compounds displayed activity on hCA II. Some derivatives ( , and ) displayed an interesting selectivity for activating hCA I over hCA II, Va, VII and XIII.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules27020545