Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro.
ChemMedChem
; 18(14): e202300206, 2023 07 17.
Article
en En
| MEDLINE
| ID: mdl-37160667
ABSTRACT
The presence of inflammatory mediators in the tumor microenvironment, such as cytokines, growth factors or eicosanoids, indicate cancer-related inflammatory processes. Targeting these inflammatory mediators and related signal pathways may offer a rational strategy for the treatment of cancer. This study focuses on the incorporation of metabolically stable, sterically demanding, and hydrophobic dicarba-closo-dodecaboranes (carboranes) into dual cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LO) inhibitors that are key enzymes in the biosynthesis of eicosanoids. The di-tert-butylphenol derivative tebufelone represents a selective dual COX-2/5-LO inhibitor. The incorporation of meta- or para-carborane into the tebufelone scaffold resulted in eight carborane-based tebufelone analogs that show no COX inhibition but 5-LO inhibitory activity inâ
vitro. Cell viability studies on HT29 colon adenocarcinoma cells revealed that the observed antiproliferative effect of the para-carborane analogs of tebufelone is enhanced by structural modifications that include chain elongation in combination with introduction of a methylene spacer resulting in higher anticancer activity compared to tebufelone. Hence, this strategy proved to be a promising approach to design potent 5-LO inhibitors with potential application as cytostatic agents.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Boranos
/
Adenocarcinoma
/
Neoplasias del Colon
Límite:
Humans
Idioma:
En
Revista:
ChemMedChem
Asunto de la revista:
FARMACOLOGIA
/
QUIMICA
Año:
2023
Tipo del documento:
Article
País de afiliación:
Alemania