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.

Effective Killing of Leukemia Cells by the Natural Product OSW-1 through Disruption of Cellular Calcium Homeostasis

“…The natural saponin molecule 3␤,16␤,17␣-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-␤-D-xylopyranosyl)-(133)-2-O-acetyl-␣-L-arabinopyranoside (OSW-1), 3 originally isolated from the bulbs of Ornithogalum saundersiae by Mimaki and co-workers (1) in 1992, has shown potent antitumor activity in various cancer cell lines including leukemia. Several studies of OSW-1 have focused on its isolation, cytotoxic tests, chemical synthesis, and preparation of synthetic analogues to understand the structure-activity relationships (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”

“…Several studies of OSW-1 have focused on its isolation, cytotoxic tests, chemical synthesis, and preparation of synthetic analogues to understand the structure-activity relationships (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). However, the mechanism by which OSW-1 exerts antitumor activity is not well delineated.…”

A ring closing metathesis strategy for carbapyranosides of xylose and arabinose

“…BH 3 .Me 2 S (0.20 mL of a 90% solution in dimethyl sulfide) was added at 0 °C, under a nitrogen atmosphere to a solution of 23 (120 mg, 0.222 mmol) in THF (7 mL) and cooled to 0 °C. The mixture was warmed to rt, stirred for an additional 1 h at this temperature, then recooled to 0 °C and treated with a mixture of 3N NaOH (0.5 mL) and 30% aqueous H 2 O 2 (0.5 mL) for 30 min.…”

Amélioration du comportement biopharmaceutique de triterpènes naturels anticancéreux par synthèse de saponines mono- et bidesmosidiques /

“…Motivés par le potentiel anticancéreux prometteur de cette saponine, différents groupes de recherche ont effectué la synthèse totale d'OSW-1 (22) durant la dernière décennie Shi et al, 2005;Xue et al, 2008]. Des études de structure-activité ont également été entreprises soit par modifications de la géminé stéroïdique [Matsuya et al, 2003;Shi et al, 2004] ou de la partie osidique Wojtkielewicz et al, 2007] afin de trouver des dérivés encore plus cytotoxiques. Ainsi, le groupe du professeur Biao Yu a complété la synthèse de plusieurs dérivés oxygénés dont la saponine 23 ( Figure 4) présentant un profil de cytotoxicité jusqu'à 25 fois supérieur à OSW-1 sur certaines lignées cancéreuses [Shi et al, 2004].…”

“…Des études de structure-activité ont également été entreprises soit par modifications de la géminé stéroïdique [Matsuya et al, 2003;Shi et al, 2004] ou de la partie osidique Wojtkielewicz et al, 2007] Une autre saponine stéroïdique, la dioscine (24, Figure 5), a attiré l'attention des chercheurs dans le domaine de la synthèse de glycosides. Cette saponine isolée d'un grand nombre de légumes et plantes de la médecine traditionnelle orientale exerce un vaste spectre d'activités biologiques (antitumorale, antivirale, antifongique et antiinflammatoire) .…”