New analogues of the potent cytotoxic saponin OSW-1.

Abstract

Saponin OSW-1 (5e-G2; 3 beta,16 beta,17 alpha-trihydroxycholest-5-en-22-one 16-O-{O-[2-O-(4-methoxybenzoyl)-beta-D-xylopyranosyl]-(1-->3)-2-O-acetyl-alpha-arabinopyranoside}) analogues: with modified side chain (5a/d-G2), 22-deoxo-23,24,25,26,27-pentanor- (14), 22-deoxo-23-oxa- (17), glycosylated with various monosaccharides (5e-G4/G6/G8), and OSW-1 structural isomer (10) were obtained. The analogues were synthesized using a previously published method for the synthesis of OSW-1. The structures of analogues were fully confirmed by spectroscopic methods, and the S-chirality at C-22 of the structural isomer was established by conformational analysis combined with the NMR spectrometry. The cytotoxicity of the analogues toward several types of malignant tumor cells was examined and compared with that of OSW-1. The results suggest that modification of the steroidal aglycone may lead to compounds with high cytotoxicity.

• Authors: Agnieszka Wojtkielewicz, Maciej Długosz, Jadwiga Maj, Jacek W Morzycki, Michał Nowakowski, Joanna Renkiewicz, Miroslav Strnad, Jana Swaczynová, Agnieszka Z Wilczewska, Jacek Wójcik
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 50 Issue 15 Pg. 3667-73 (Jul 26 2007) ISSN: 0022-2623 [Print] United States
• PMID: 17608396 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cholestenones
• Saponins
• OSW 1

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Line, Tumor
• Cholestenones (chemical synthesis, chemistry, pharmacology)
• Drug Screening Assays, Antitumor
• Humans
• Magnetic Resonance Spectroscopy
• Models, Molecular
• Molecular Conformation
• Saponins (chemical synthesis, chemistry, pharmacology)
• Stereoisomerism
• Structure-Activity Relationship