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

• Published in: Bioorganic & medicinal chemistry 2014-01, Vol.22 (1), p.585-593
• Main Authors: Salomatina, Oksana V., Markov, Andrey V., Logashenko, Evgeniya B., Korchagina, Dina V., Zenkova, Marina A., Salakhutdinov, Nariman F., Vlassov, Valentin V., Tolstikov, Genrikh A.
• Format: Article
• Language: English
• Subjects: Biological activity; Cell Proliferation; Cytotoxicity; Glycyrrhetinic Acid - analogs & derivatives; Glycyrrhetinic Acid - chemical synthesis; Glycyrrhetinic Acid - chemistry; Glycyrrhetinic acid derivatives; Humans; Lipopolysaccharides; Neoplasms - chemistry; Nitric oxide; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - chemistry; Selectivity index; Structure-Activity Relationship
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2013.10.049

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.