Carborane-Based Tebufelone Analogs and Their Biological Evaluation In Vitro
Publikation: Beitrag in Fachzeitschrift › Forschungsartikel › Beigetragen › Begutachtung
Beitragende
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 in 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.
Details
Originalsprache | Englisch |
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Aufsatznummer | e202300206 |
Fachzeitschrift | ChemMedChem |
Jahrgang | 18 |
Ausgabenummer | 14 |
Publikationsstatus | Veröffentlicht - 17 Juli 2023 |
Peer-Review-Status | Ja |
Externe IDs
PubMed | 37160667 |
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Schlagworte
Ziele für nachhaltige Entwicklung
ASJC Scopus Sachgebiete
Schlagwörter
- bioisosteric replacement, cancer, carboranes, cyclooxygenase, lipoxygenase, tebufelone