New analogues of the potent cytotoxic saponin OSW-1.
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.
Wojtkielewicz
Agnieszka
A
Institute of Chemistry, University of Białystok, al. Pilsudskiego 11/4, 15-443 Bialystok, Poland. jeremy@uwb.edu.pl
Długosz
Maciej
M
Maj
Jadwiga
J
Morzycki
Jacek W
JW
Nowakowski
Michał
M
Renkiewicz
Joanna
J
Strnad
Miroslav
M
Swaczynová
Jana
J
Wilczewska
Agnieszka Z
AZ
Wójcik
Jacek
J
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002783:Cholestenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D012503:Saponins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002783:Cholestenones; D012503:Saponins; C106408:OSW 1