title: Synthesis and antitumor activity of ring A modified glycyrrhetinic acid derivatives.
abstract: 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 IC(50) between 1.96 and 5.14 μm for five human cancer cell lines and triggers apoptosis in 80% of the cells.
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str 2, D-06120 Halle, Saale, Germany. rene.csuk@chemie.uni-halle.de
authors.forename: René
authors.initials: R
authors.lastname: Csuk
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.forename: Ralph
authors.initials: R
authors.lastname: Kluge
authors.forename: Dieter
authors.initials: D
authors.lastname: Ströhl
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50
chemical_list: D000970:Antineoplastic Agents; D006034:Glycyrrhetinic Acid