Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors.
J Enzyme Inhib Med Chem
; 38(1): 2191165, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-36938694
ABSTRACT
In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a-19a and 1b-19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Selenio
/
Inhibidores de Anhidrasa Carbónica
/
Anhidrasas Carbónicas
/
Neoplasias
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
España