New Analogues of the Potent Cytotoxic Saponin OSW-1

• Published in: Journal of medicinal chemistry Vol. 50; no. 15; pp. 3667 - 3673
• Main Authors: Wojtkielewicz, Agnieszka, Długosz, Maciej, Maj, Jadwiga, Morzycki, Jacek W, Nowakowski, Michał, Renkiewicz, Joanna, Strnad, Miroslav, Swaczynová, Jana, Wilczewska, Agnieszka Z, Wójcik, Jacek
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 26.07.2007; Amer Chemical Soc
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Chemistry, Medicinal; Cholestenones - chemical synthesis; Cholestenones - chemistry; Cholestenones - pharmacology; Drug Screening Assays, Antitumor; General aspects; Humans; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Miscellaneous; Models, Molecular; Molecular Conformation; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Saponins - chemical synthesis; Saponins - chemistry; Saponins - pharmacology; Science & Technology; Stereoisomerism; Structure-Activity Relationship; SIDE-CHAINS; ORNITHOGALUM-SAUNDERSIAE; CYTOSTATIC ACTIVITY; ANTITUMOR SAPONIN; EFFICIENT SYNTHESIS; INTACT SKELETON; NATURAL PRODUCT OSW-1; CHOLESTANE GLYCOSIDES; AGLYCONE; MOLECULAR-MECHANICS; Antineoplastic agent; Steroid; Conformational analysis; Cytotoxicity; In vitro; Biological activity; Disaccharide; Saponin; Chemical modification; Side chain; Cholestane derivatives; Glycoside; Chemical synthesis
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm0613572

Saponin OSW-1 (5e-G2; 3β,16β,17α-trihydroxycholest-5-en-22-one 16-O-{O-[2-O-(4-methoxybenzoyl)-β-d-xylopyranosyl]-(1→3)-2-O-acetyl-α-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.