The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms

Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine / Niccolò Chiaramonte, Soumia Maach, Caterina Biliotti, Andrea Angeli, Gian luca Bartolucci, Laura Braconi, Silvia Dei, Elisabetta Teodori, Claudiu T. Supuran, Maria Novella Romanelli. - In: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY. - ISSN 1475-6366. - STAMPA. - 35:(2020), pp. 1003-1010. [10.1080/14756366.2020.1749602]

Synthesis and carbonic anhydrase activating properties of a series of 2-amino-imidazolines structurally related to clonidine

Niccolò Chiaramonte;Soumia Maach;Caterina Biliotti;Andrea Angeli;Gian luca Bartolucci;Laura Braconi;Silvia Dei;Elisabetta Teodori;Claudiu T. Supuran;Maria Novella Romanelli
2020

Abstract

The Carbonic Anhydrase (CA, EC 4.2.1.1) activating properties of histamine have been known for a long time. This compound has been extensively modified but only in few instances the imidazole ring has been replaced with other heterocycles. It was envisaged that the imidazoline ring could be a bioisoster of the imidazole moiety. Indeed, we report that clonidine, a 2-aminoimidazoline derivative, was found able to activate several human CA isoforms (hCA I, IV, VA, VII, IX, XII and XIII), with potency in the micromolar range, while it was inactive on hCA II. A series of 2-aminoimidazoline, structurally related to clonidine, was then synthesised and tested on selected hCA isoforms. The compounds were inactive on hCA II while displayed activating properties on hCA I, VA, VII and XIII, with KA values in the micromolar range. Two compounds (10 and 11) showed some preference for the hCA VA or VII isoforms
2020
35
1003
1010
Goal 3: Good health and well-being for people
Niccolò Chiaramonte, Soumia Maach, Caterina Biliotti, Andrea Angeli, Gian luca Bartolucci, Laura Braconi, Silvia Dei, Elisabetta Teodori, Claudiu T. Supuran, Maria Novella Romanelli
File in questo prodotto:
File Dimensione Formato  
134_JEIMC2020_imidazoline.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 1.78 MB
Formato Adobe PDF
1.78 MB Adobe PDF

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1192313
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 5
social impact