title: Incorporation of a Michael acceptor enhances the antitumor activity of triterpenoic acids.
abstract: Finding and developing drugs for the treatment of cancer has been challenging scientists for many decades, and using compounds of natural origin represents one of several strategies. Triterpenoic acids are a very promising class of secondary metabolites being able to induce apoptosis while their cytotoxicity is low. Therefore, derivatizations have to be conducted to improve cytotoxicity while retaining their ability to induce programmed cell death. The incorporation of a Michael acceptor into molecules resulted very often in drugs of improved cytotoxicity. Thus, in this study we synthesized and evaluated several Michael acceptor substituted compounds derived from glycyrrhetinic, ursolic, oleanolic and platanic acid. The influence of the presence of such a functional group onto the cytotoxicity was investigated in colorimetric sulforhodamine B assays employing several human cancer cell lines. EC50 values in the single-digit micromolar range were measured. Thus, the incorporation of a Michael acceptor unit into triterpenoic acids enhances the cytotoxicity of these compounds significantly.
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany.
authors.forename: Lucie
authors.initials: L
authors.lastname: Heller
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany.
authors.forename: Vincent
authors.initials: V
authors.lastname: Perl
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Köwitsch
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str.2, D-06120 Halle (Saale), Germany.
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Organic Chemistry, 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: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes
keywords: Glycyrrhetinic acid; Oleanolic acid; Platantic acid; Triterpenoic acid; Tumor cells; Ursolic acid