Synthesis and evaluation of cytotoxic and Na+/K+-ATP-ase inhibitory activity of selected 5α-oleandrigenin derivatives

  • Eur J Med Chem. 2019 Oct 15:180:417-429. doi: 10.1016/j.ejmech.2019.07.028.
Karol Michalak  1 ,  Lucie Rárová  2 ,  Martin Kubala  3 ,  Petra Čechová  4 ,  Miroslav Strnad  5 ,  Jerzy Wicha  6
Affiliations
  • 1. Institute of Organic Chemistry, Polish Academy of Sciences, ul. Marcina Kasprzaka 44/52, 01-224, Warsaw, Poland.
  • 2. Laboratory of Growth Regulators, Institute of Experimental Botany ASCR & Palacky University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic.
  • 3. Department of Biophysics, Faculty of Science, Palacky University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic; Department of Experimental Physics, Faculty of Science, Palacky University, 17. listopadu 12, 771 46, Olomouc, Czech Republic.
  • 4. Department of Biophysics, Faculty of Science, Palacky University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic; Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17. listopadu 12, 771 46, Olomouc, Czech Republic.
  • 5. Laboratory of Growth Regulators, Institute of Experimental Botany ASCR & Palacky University, Šlechtitelů 27, 783 71, Olomouc, Czech Republic. Electronic address: [email protected].
  • 6. Institute of Organic Chemistry, Polish Academy of Sciences, ul. Marcina Kasprzaka 44/52, 01-224, Warsaw, Poland. Electronic address: [email protected].
PMID: 31325787 DOI: 10.1016/j.ejmech.2019.07.028
Abstract

Oleandrin, the major biologically active constituent of shrub Nerium oleander preparations of which have been used in traditional Mediterranean and Asian medicine, attracts a great deal of attention due to its pronounced Anticancer activity. The synthesis of oleandrigenin model, 16β-hydroxy-3β-methoxy-5α-card-20(22)-enolide 16-acetate, from androstenolone acetate through 17β-(3-furyl)-intermediates has been developed. Several related 17β-(butenolidyl)- and 17β-(furyl)-androstane derivatives were synthesized and tested for in vitro cytotoxic and Na+/K+-ATP-ase inhibitory activities. Comparison of Na+/K+-ATP-ase inhibitory and cytotoxic activity underlines complex nature of the relationship.

Keywords
ATP-ase inhibition; Cardenolides; Cytotoxicity; Furan transformation; Partial synthesis.