Exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors.
Liliana LucescuAlina GhinetSergiu ShovaRomain MagnezXavier ThuruAmaury FarceBenoît RigoDalila BeleiJoëlle DuboisElena BîcuPublished in: Archiv der Pharmazie (2019)
Unprecedented triazinyl-isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2-ethynyl-4,6-dimethoxy-1,3,5-triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine-isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin-2-one was detrimental to the inhibitory activity while the pyrrolidin-2-thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP-CAAX was also evaluated.
Keyphrases
- endothelial cells
- induced pluripotent stem cells
- induced apoptosis
- pluripotent stem cells
- solid phase extraction
- transcription factor
- human health
- cell cycle arrest
- signaling pathway
- small molecule
- oxidative stress
- quantum dots
- risk assessment
- mass spectrometry
- gold nanoparticles
- binding protein
- highly efficient
- cell death
- reduced graphene oxide
- pi k akt
- structure activity relationship