Design, Synthesis, and Cancer Cell Growth Inhibitory Activity of Triphenylphosphonium Derivatives of the Triterpenoid Betulin.
Olga V TsepaevaAndrey V NemtarevTimur I AbdullinLeysan R Grigor'evaElena V KuznetsovaRezeda A AkhmadishinaLiliya Eugenevna ZiganshinaHanh H CongVladimir F MironovPublished in: Journal of natural products (2017)
A series of new triphenylphosphonium (TPP) derivatives of the triterpenoid betulin (1, 3-lup-20(29)-ene-3β,28-diol) have been synthesized and evaluated for cytotoxic effects against human breast cancer (MCF-7), prostate adenocarcinoma (PC-3), vinblastine-resistant human breast cancer (MCF-7/Vinb), and human skin fibroblast (HSF) cells. The TPP moiety was applied as a carrier group through the acyl linker at the 28- or 3- and 28-positions of betulin to promote cellular and mitochondrial accumulation of the resultant compounds. A structure-activity relationship study has revealed the essential role of the TPP group in the biological properties of the betulin derivatives produced. The present results showed that a conjugate of betulin with TPP (3) enhanced antiproliferative activity toward vinblastine-resistant MCF-7 cells, with an IC50 value as low as 0.045 μM.
Keyphrases
- structure activity relationship
- induced apoptosis
- endothelial cells
- breast cancer cells
- cell cycle arrest
- prostate cancer
- oxidative stress
- induced pluripotent stem cells
- endoplasmic reticulum stress
- squamous cell carcinoma
- signaling pathway
- radiation therapy
- cancer therapy
- single cell
- drug delivery
- heat shock
- squamous cell
- oxide nanoparticles