Synthesis of novel 2-cyano substituted glycyrrhetinic acid derivatives as inhibitors of cancer cells growth and NO production in LPS-activated J-774 cells

  • Bioorg Med Chem. 2014 Jan 1;22(1):585-93. doi: 10.1016/j.bmc.2013.10.049.
Oksana V Salomatina  1 ,  Andrey V Markov  2 ,  Evgeniya B Logashenko  3 ,  Dina V Korchagina  1 ,  Marina A Zenkova  2 ,  Nariman F Salakhutdinov  1 ,  Valentin V Vlassov  2 ,  Genrikh A Tolstikov  1
Affiliations
  • 1. N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch Russian Academy of Sciences, 9, Lavrentiev ave., Novosibirsk 630090, Russian Federation.
  • 2. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrentiev ave., Novosibirsk 630090, Russian Federation.
  • 3. Institute of Chemical Biology and Fundamental Medicine, Siberian Branch Russian Academy of Sciences, 8, Lavrentiev ave., Novosibirsk 630090, Russian Federation. Electronic address: [email protected].
PMID: 24268542 DOI: 10.1016/j.bmc.2013.10.049
Abstract

Here we report the synthesis and biological activity of new semi-synthetic derivatives of naturally occurring glycyrrhetinic acid bearing a 2-cyano-3-oxo-1-en moiety in the A-ring and double bonds and carbonyl groups in the C, D and E rings. Bioassays using murine macrophage-like and tumor cells show that compound 4, which differs from Soloxolone methyl by the absence of a 9(11)-double bond in the C-ring, displays anti-inflammatory and inhibitory activities with respect to tumor cells with a high selectivity index value.

Keywords
Biological activity; Cytotoxicity; Glycyrrhetinic acid derivatives; Nitric oxide; Selectivity index.