Carbonic anhydrases (CAs) continue to represent a relevant pharmaceutical target. The need of selective inhibitors and the involvement of these metalloenzymes in many multifaceted diseases boost the search for new ligands able to distinguish among the different CA isoforms, and for multifunctional systems simultaneously able to inhibit CAs and to interfere with other pathological events by interacting with additional targets. In this work, we successfully explored the possibility of preparing new CAs ligands by combining calixarenes with benzensulfonamide units. Inhibition tests towards three human CA isoforms evidenced, for some of the ligands, Ki values in the nanomolar range and promising selectivity. X-ray and molecular modeling studies provided information on the mode of binding of these calixarene derivatives. Thanks to the encouraging results and the structural features typical of the calixarene scaffold, it is then possible to plan for the future the design of multifunctional inhibitors for this class of widely spread enzymes.

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition / Sbravati, Davide; Bonardi, Alessandro; Bua, Silvia; Angeli, Andrea; Ferraroni, Marta; Nocentini, Alessio; Casnati, Alessandro; Gratteri, Paola; Sansone, Francesco; Supuran, Claudiu T. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 28:6(2022), p. e202103527. [10.1002/chem.202103527]

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition

Sbravati, Davide;Casnati, Alessandro;Sansone, Francesco;
2022

Abstract

Carbonic anhydrases (CAs) continue to represent a relevant pharmaceutical target. The need of selective inhibitors and the involvement of these metalloenzymes in many multifaceted diseases boost the search for new ligands able to distinguish among the different CA isoforms, and for multifunctional systems simultaneously able to inhibit CAs and to interfere with other pathological events by interacting with additional targets. In this work, we successfully explored the possibility of preparing new CAs ligands by combining calixarenes with benzensulfonamide units. Inhibition tests towards three human CA isoforms evidenced, for some of the ligands, Ki values in the nanomolar range and promising selectivity. X-ray and molecular modeling studies provided information on the mode of binding of these calixarene derivatives. Thanks to the encouraging results and the structural features typical of the calixarene scaffold, it is then possible to plan for the future the design of multifunctional inhibitors for this class of widely spread enzymes.
Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition / Sbravati, Davide; Bonardi, Alessandro; Bua, Silvia; Angeli, Andrea; Ferraroni, Marta; Nocentini, Alessio; Casnati, Alessandro; Gratteri, Paola; Sansone, Francesco; Supuran, Claudiu T. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - 28:6(2022), p. e202103527. [10.1002/chem.202103527]
File in questo prodotto:
File Dimensione Formato  
post print manuscript Sansone.pdf

embargo fino al 10/01/2023

Descrizione: manuscript
Tipologia: Documento in Post-print
Licenza: Creative commons
Dimensione 718.75 kB
Formato Adobe PDF
718.75 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Chemistry Carbonic Anhydrases 2021 SI.pdf

accesso aperto

Descrizione: Materiale supplementare
Tipologia: Versione (PDF) editoriale
Licenza: Creative commons
Dimensione 4 MB
Formato Adobe PDF
4 MB Adobe PDF Visualizza/Apri

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

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/2907677
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact