title: A "natural" approach: synthesis and cytoxicity of monodesmosidic glycyrrhetinic acid glycosides.
abstract: Several pentacyclic triterpenoic acids have shown noteworthy antitumor activity, among them betulinic acid as well as oleanolic acid and derivatives thereof. Glycyrrhetinic acid (GA) exhibits some cytotoxic activity albeit this compound is not as active as betulinic acid, but GA came in the focus of scientific interest since it triggers apoptosis in tumor cells. In addition, it can be extracted from the roots of liquorice in high yields. Previous studies revealed that the introduction of an extra hydrophilic moiety increases the cytotoxicity of these compounds. Thus, a series of GA glycosides was prepared utilizing hexoses as well as pentoses (in D- and L-configuration) by using glycosyl trichloroacetimidates and TMSOTf as catalyst. The compounds were screened for cytotoxic activity against seven human cancer cell lines and the not malignant murine cell line NIH 3T3using a photometric SRB assay. The compounds trigger apoptosis as shown from extra trypan blue and acridine orange/ethidium bromide staining.
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Saale, Germany; Faculdade de Ciências, Universidade de Lisboa, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Saale, Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.affiliation: Faculdade de Ciências, Universidade de Lisboa, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal.
authors.forename: Nuno M
authors.initials: NM
authors.lastname: Xavier
authors.affiliation: Faculdade de Ciências, Universidade de Lisboa, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal.
authors.forename: Ana R
authors.initials: AR
authors.lastname: Jesus
authors.affiliation: Faculdade de Ciências, Universidade de Lisboa, Centro de Química e Bioquímica/Departamento de Química e Bioquímica, Campo Grande, Ed. C8, Piso 5, 1749-016 Lisboa, Portugal.
authors.forename: Amélia P
authors.initials: AP
authors.lastname: Rauter
authors.affiliation: Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Saale, Germany. Electronic address: rene.csuk@chemie.uni-halle.de.
authors.forename: René
authors.initials: R
authors.lastname: Csuk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006034:Glycyrrhetinic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008968:Molecular Conformation; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D006034:Glycyrrhetinic Acid
keywords: Antitumor compounds; Apoptosis; Glycosylation; Glycyrrhetinic acid; SRB assay; Trypan blue staining