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 D.; Bonardi A.; Bua S.; Angeli A.; Ferraroni M.; Nocentini A.; Casnati A.; Gratteri P.; Sansone F.; Supuran C.T.. - In: CHEMISTRY-A EUROPEAN JOURNAL. - ISSN 0947-6539. - ELETTRONICO. - 28:(2022), pp. 1-8. [10.1002/chem.202103527]

Calixarenes Incorporating Sulfonamide Moieties: Versatile Ligands for Carbonic Anhydrases Inhibition

Bonardi A.
Membro del Collaboration Group
;
Bua S.
Membro del Collaboration Group
;
Angeli A.
Membro del Collaboration Group
;
Ferraroni M.
Membro del Collaboration Group
;
Nocentini A.
Membro del Collaboration Group
;
Gratteri P.
;
Sansone F.
;
Supuran C. T.
Funding Acquisition
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.
2022
28
1
8
Goal 3: Good health and well-being
Sbravati D.; Bonardi A.; Bua S.; Angeli A.; Ferraroni M.; Nocentini A.; Casnati A.; Gratteri P.; Sansone F.; Supuran C.T.
File in questo prodotto:
File Dimensione Formato  
Chemistry A European J - 2021 - Sbravati - Calixarenes Incorporating Sulfonamide Moieties Versatile Ligands for Carbonic.pdf

accesso aperto

Tipologia: Pdf editoriale (Version of record)
Licenza: Open Access
Dimensione 2.94 MB
Formato Adobe PDF
2.94 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/2158/1257029
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 2
  • ???jsp.display-item.citation.isi??? 2
social impact