Synthesis of furanotriterpenoids from betulin and evaluation of Tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibitory properties of new semi-synthetic triterpenoids.
Eur J Med Chem
; 276: 116724, 2024 Oct 05.
Article
de En
| MEDLINE
| ID: mdl-39079310
ABSTRACT
For the first time, a synthetic route for preparing lupane and oleanane derivatives with a hydrogenated furan ring as a cycle A of triterpene scaffold is described. Most of the synthesized compounds, furanoterpenoids and their synthetic intermediates, were non-toxic against the tested cancer and non-cancerous cell lines, and evinced significant inhibitory activity with IC50 1.0-9.0 µM in the tyrosyl-DNA phosphodiesterase 1 (Tdp1) inhibition test. Lupane derivatives - 1-oxime 7, 1,10-seco-hydroxynitrile 11 and furanoterpenoid 14 - were selected as those expected to be the most promising compounds. The results of molecular modeling evinced the strongest binding of compound 11 to the active site of Tdp1 compared to the reference drug. Simultaneously, only compound 11 at subtoxic concentration (10 µM) produced a synergetic effect on the topotecan activity against HeLa-V cells.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Inhibiteurs de la phosphodiestérase
/
Triterpènes
/
Phosphodiesterases
/
Relation dose-effet des médicaments
Limites:
Humans
Langue:
En
Journal:
Eur J Med Chem
/
Eur. j. med. chem
/
European journal of medicinal chemistry
Année:
2024
Type de document:
Article
Pays d'affiliation:
Russie
Pays de publication:
France