N-Substituted and ring opened saccharin derivatives selectively inhibit transmembrane, tumor-associated carbonic anhydrases IX and XII.
Bioorg Med Chem
; 25(13): 3583-3589, 2017 07 01.
Article
en En
| MEDLINE
| ID: mdl-28416101
ABSTRACT
A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl moieties, as well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides is unknown for the moment, the good efficacy and especially selectivity for the inhibition of the tumor-associated over the cytosolic, widespread isoforms, make these derivatives of considerable interest as enzyme inhibitors with various pharmacologic applications.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Sacarina
/
Inhibidores de Anhidrasa Carbónica
/
Anhidrasas Carbónicas
/
Anhidrasa Carbónica IX
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2017
Tipo del documento:
Article
País de afiliación:
Letonia