A novel route to a chiral building block for the preparation of cyclopentenyl carbocyclic nucleosides. Synthesis and anticancer activity of enantiomeric neplanocins A.
Beata ŁukasikMaciej MikinaMarian MikołajczykRóża PawłowskaRemigiusz ŻurawińskiPublished in: RSC advances (2020)
The synthesis of both enantiomers of 3-[( tert -butyldimethylsilyl)oxy]methyl-4,5- O -isopropylidenecyclopent-2-en-1-ol was accomplished in six steps based on optically inactive dimethyl meso -tartrate. This key intermediate in the synthesis of cyclopentenyl carbocyclic nucleosides was subsequently applied in the preparation of enantiomeric neplanocins A. The toxic effect of these compounds was investigated for a series of suspension and adherent cancer cell lines and normal human fibroblasts. (-)-Neplanocin A ((-)-NPA) was more toxic against all tested cancer cell lines than its dextrorotary counterpart. The highest toxicity with IC 50 values of 7 and 10 μM was observed for the MOLT-4 and A431 cells, respectively. Moreover, (-)-NPA also induced apoptosis in A431 cell while this effect was not observed for (+)-NPA.
Keyphrases
- induced apoptosis
- endoplasmic reticulum stress
- oxidative stress
- papillary thyroid
- signaling pathway
- capillary electrophoresis
- squamous cell
- endothelial cells
- molecularly imprinted
- single cell
- stem cells
- cell therapy
- lymph node metastasis
- squamous cell carcinoma
- mass spectrometry
- childhood cancer
- cell cycle arrest
- cell death
- young adults
- atomic force microscopy
- ionic liquid
- oxide nanoparticles