title: Synthesis, encapsulation and antitumor activity of new betulin derivatives.
abstract: Novel betulin derivatives were prepared and tested for their antitumor activity. Starting from 3-O-acetyl- or 3-O-methyl-betulinic aldehyde, the synthesis of C-28 ethynyl derivatives was performed; their subsequent transformation with several 1,3-dipolarophiles afforded pyrazoles and 1,2,3-triazoles. Their screening for antitumor activity was performed in a panel of 15 human cancer cell lines by a colorimetric SRB-assay. Thereby, several compounds revealed a higher cytotoxicity than betulinic acid. In addition, the encapsulation of the lead structure 7 into liposomes was investigated. The results from a dye exclusion test and from DNA laddering experiments provided evidence for an apoptotic cell death.
authors.affiliation: Martin-Luther-Universität Halle-Wittenberg, Organische Chemie, Halle (Saale), Germany. rene.csuk@chemie.uni-halle.de
authors.forename: René
authors.initials: R
authors.lastname: Csuk
authors.forename: Alexander
authors.initials: A
authors.lastname: Barthel
authors.forename: Ronny
authors.initials: R
authors.lastname: Sczepek
authors.forename: Bianka
authors.initials: B
authors.lastname: Siewert
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwarz
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003124:Colorimetry / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D008081:Liposomes; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D053978:Pentacyclic Triterpenes; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012235:Rhodamines / Q000737:chemistry; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D005456:Fluorescent Dyes; D008081:Liposomes; D053978:Pentacyclic Triterpenes; D011720:Pyrazoles; D012235:Rhodamines; D014230:Triazoles; D014315:Triterpenes; C022027:lissamine rhodamine B; C002503:betulin; D000094062:Betulinic Acid