title: Rhodamine B conjugates of triterpenoic acids are cytotoxic mitocans even at nanomolar concentrations.
abstract: Triterpenoic acids 1-6 exhibited very low or no cytotoxicity at all, but their corresponding 2,3-di-O-acetyl-piperazinyl amides 13-18 showed low EC50values for several human tumor cell lines. Their cytotoxicity, however, was also high for the non-malignant mouse fibroblasts NIH 3T3. A significant improvement was achieved by preparing the rhodamine B derivatives 19-24. While rhodamine B is not cytotoxic (up to a concentration of 30μM - cut-off of the assay), the triterpenoid piperazine-spacered rhodamine B derivatives were cytotoxic in nano-molar concentration. Compound 24 (a diacetylated maslinic acid derivative) was most toxic for several human tumor cell lines but less toxic for mouse fibroblasts NIH 3T3. Staining and double-staining experiments revealed 24 to act as a mitocan.
authors.affiliation: Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Sven
authors.initials: S
authors.lastname: Sommerwerk
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: Christoph
authors.initials: C
authors.lastname: Kerzig
authors.affiliation: Martin-Luther University Halle-Wittenberg, Organic Chemistry, Kurt-Mothes-Str. 2, D-06120 Halle (Saale), Germany.
authors.forename: Annemarie E
authors.initials: AE
authors.lastname: Kramell
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: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D008928:Mitochondria / Q000187:drug effects*; D041681:NIH 3T3 Cells; D012235:Rhodamines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*
chemical_list: D012235:Rhodamines; D014315:Triterpenes; C029773:rhodamine B
keywords: Betulinic acid; Cytotoxicity; Glycyrrhetinic acid; Maslinic acid; Mitocan; Oleanolic acid; Platanic acid; Rhodamine B; Triterpenes; Ursolic acid