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. Betulin derivatives bearing an ethynyl side chain were synthesized. These compounds possess quite promising antitumor activity by triggering apoptosis. Encapsulation in liposomes is investigated. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.