Synthesis, characterization and in vitro anti-neoplastic activity of gypsogenin derivatives

Gypsogenin (L-1; 3-hydroxy-23-oxoolean-12-en-28-oic acid), a natural saponin, was isolated from the boiling water extract of Gypsophila arrostii roots. In addition, the derivatives gypsogenin thiosemicarbazone (L-2; 23-[(aminocarbonothioyl)hydrazono]-3-hydroxolean-12-en-28-oic acid) and gypsogenin thiosemicarbazone glyoxime ((LH2)-H-3; (3 beta)-3-hydroxy-23-[({[(1Z,2E)-N-hydroxy-2-(hydroxyimino)ethanimidoyl]amino}carbonothioyl)hydrazono] olean-12-en-28-oic acid) as well as the Cu(II) and Co(II) complexes of (LH2)-H-3 were prepared. The structures were established on NMR analysis (H-1, C-13 NMR, HMBC, HMQC, and NOESY), FT-IR and completed by analysis of LC/MS. Furthermore, the antiproliferative effects of the Co(II) and Cu(II) complexes of the gypsogenin derivatives were assayed in human promyelocytic leukemia (HL 60) cells. These complexes were found to be potent anticancer agents with concentrations that inhibited 50% of proliferation (IpC50) between 5 mu M and 40 mu M. Cell death was distinguished by HO/PI double staining. The Co(II) complex of (LH2)-H-3 has shown approximately %50 apoptotic effect at 10 mu M concentration. Paclitaxel has been used as positive control. (C) 2013 Elsevier Inc. All rights reserved.