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 (L(3)H2; (3β)-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 L(3)H2 were prepared. The structures were established on NMR analysis ((1)H, (13)C 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 5μM and 40μM. Cell death was distinguished by HO/PI double staining. The Co(II) complex of L(3)H2 has shown approximately %50 apoptotic effect at 10μM concentration. Paclitaxel has been used as positive control.
Chemistry Department, Faculty of Science, Ege University, Bornova, İzmir 35100, Turkey.
Safiye
S
Emirdağ-Öztürk
Chemistry Department, Adnan Menderes University, Aydin 09010, Turkey. Electronic address: ilknurbabahan@yahoo.com.
İlknur
İ
Babahan
Biology Department, Adnan Menderes University, Aydin 09010, Turkey.
Ali
A
Özmen
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry*; D013882:Thiosemicarbazones / Q000737:chemistry
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D012503:Saponins; D013882:Thiosemicarbazones; D003035:Cobalt; D003300:Copper
Antiproliferative; Gypsogenin; Leukemia; Thiosemicarbazone; Transition metal complex; vic-Dioxime