Synthesis, cytotoxicity and liposome preparation of 28-acetylenic betulin derivatives.
Several novel betulin derivatives were prepared and evaluated for their antitumor activity. 3-O-acetylbetulinic aldehyde served as an ideal starting material for the synthesis of 28-acetylenic derivatives. These compounds were further transformed into pyrazoles and 1,2,3-triazoles. Also, the synthesis of 3-amino substituted butenolides was carried out. The compounds were screened for their antitumor activity in a panel of 15 human cancer cell lines in a sulforhodamine B (SRB) assay. Several compounds showed a noteworthy antitumor activity. In addition, the possibility of encapsulation into liposomes was examined, thereby resulting in an increased cytotoxicity. The results from a trypan-blue test and from DNA laddering provided evidence for an apoptotic cell death.
Csuk
René
R
Bereich Organische Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Str. 2, D-06120 Halle, Saale, Germany. rene.csuk@chemie.uni-halle.de
Barthel
Alexander
A
Kluge
Ralph
R
Ströhl
Dieter
D
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000094062:Betulinic Acid
D000970:Antineoplastic Agents; D008081:Liposomes; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid