Synthesis and antitumor activity of ring A modified glycyrrhetinic acid derivatives

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• 作者：René ; Csuk ; ^{rene.csuk@chemie.uni-halle.de} ; Stefan Schwarz ; Bianka Siewert ; Ralph Kluge ; Dieter Strö ; hl
• 关键词：Glycyrrhetinic acid ; Antitumor activity ; Apoptosis
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：November, 2011
• 年：2011
• 卷：46
• 期：11
• 页码：5356-5369
• 全文大小：791 K

文摘

Triterpenoic acids show many pharmacological effects, among them an antiinflammatory or an antitumor activity. One of these, glycyrrhetinic acid (1) is of interest because of its antitumor profile. Glycyrrhetinic acid is not only cytotoxic but also triggers apoptosis in various human tumor cell lines. To improve the cytotoxicity of parent 1 we set out to synthesize new derivatives of it - differing in structure and lipophilicity. These compounds were tested in a sulforhodamine B assay for cytotoxicity, and screened for their ability to induce apoptosis using an acridine orange/ethidium bromide assay and trypan blue staining. The most active compound, 34, a benzyl glycyrrhetinate holding an extra 3-N-(3-aminopropyl)glycyl substituent showed IC₅₀ between 1.96 and 5.14?¦Ìm for five human cancer cell lines and triggers apoptosis in 80 % of the cells.