Herein we report the synthesis of a new series of aromatic sulfamates investigated for the inhibition of four human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IV, and IX. The reported derivatives, obtained by a sulfamoylation reaction of the corresponding phenolic precursors, bear arylthiazolin-4-one moieties as spacers between the benzenesulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Thiazolin-4-ones are biologically privileged scaffolds, endowed with versatile biological activity, such as an anti-proliferative action. Phenolic precursors, also evaluated for CA inhibition, did not exhibit noteworthy efficacy in inhibiting the screened hCAs, whereas low nanomolar inhibitors were evidenced within the sulfamates subset mainly against hCA II (KIs in the range of 28.7-84.3 nM) and IX (KIs in the range of 17.6-73.3 nM). The variety of substituents appended at the outer aromatic portion almost generally reduced the inhibitory efficacy against isoforms II and IV, increasing instead that against the tumor-associated isoform IX.

Discovery of thiazolin-4-one-based aromatic sulfamates as a new class of carbonic anhydrase isoforms I, II, IV, and IX inhibitors / Nocentini, Alessio; Moi, Davide; Balboni, Gianfranco; Onnis, Valentina; Supuran, Claudiu T. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - ELETTRONICO. - 77:(2018), pp. 293-299. [10.1016/j.bioorg.2018.01.023]

Discovery of thiazolin-4-one-based aromatic sulfamates as a new class of carbonic anhydrase isoforms I, II, IV, and IX inhibitors

Nocentini, Alessio
;
Supuran, Claudiu T
2018

Abstract

Herein we report the synthesis of a new series of aromatic sulfamates investigated for the inhibition of four human (h) isoforms of zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1), hCA I, II, IV, and IX. The reported derivatives, obtained by a sulfamoylation reaction of the corresponding phenolic precursors, bear arylthiazolin-4-one moieties as spacers between the benzenesulfamate fragment which binds the zinc ion from the active site, and the tail of the inhibitor. Thiazolin-4-ones are biologically privileged scaffolds, endowed with versatile biological activity, such as an anti-proliferative action. Phenolic precursors, also evaluated for CA inhibition, did not exhibit noteworthy efficacy in inhibiting the screened hCAs, whereas low nanomolar inhibitors were evidenced within the sulfamates subset mainly against hCA II (KIs in the range of 28.7-84.3 nM) and IX (KIs in the range of 17.6-73.3 nM). The variety of substituents appended at the outer aromatic portion almost generally reduced the inhibitory efficacy against isoforms II and IV, increasing instead that against the tumor-associated isoform IX.
77
293
299
Nocentini, Alessio; Moi, Davide; Balboni, Gianfranco; Onnis, Valentina; Supuran, Claudiu T
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in FLORE 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: https://hdl.handle.net/2158/1289785
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact