Design, Synthesis, and Cancer Cell Growth Inhibitory Activity of Triphenylphosphonium Derivatives of the Triterpenoid Betulin

  • J Nat Prod. 2017 Aug 25;80(8):2232-2239. doi: 10.1021/acs.jnatprod.7b00105.
Olga V Tsepaeva  1 ,  Andrey V Nemtarev  1  2 ,  Timur I Abdullin  2 ,  Leysan R Grigor'eva  2 ,  Elena V Kuznetsova  2 ,  Rezeda A Akhmadishina  2 ,  Liliya E Ziganshina  2 ,  Hanh H Cong  2 ,  Vladimir F Mironov  1  2
Affiliations
  • 1. A. E. Arbuzov Institute of Organic and Physical Chemistry, Kazan Scientific Center, Russian Academy of Sciences , Arbuzov Street 8, 420088, Kazan, Russian Federation.
  • 2. Kazan (Volga Region) Federal University , Kremlevskaya Street 18, 420008, Kazan, Russian Federation.
PMID: 28782948 DOI: 10.1021/acs.jnatprod.7b00105
Abstract

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.