Synthesis of lupane-type saponins bearing mannosyl and 3,6-branched trimannosyl residues and their evaluation as anticancer agents.
The saponins modified with mono- or trimannosyl residues can provide a convenient means of delivering drugs to certain human cells via interactions with mannose receptors. In the study reported therein, we developed a convenient approach for the synthesis of 3-O-mannoside and branched trimannoside derivatives of the saponin lupeol and of C-28 acyl esters of 3-O-acetyl-betulinic acid bearing the same mannosyl entities. Lupeol and 3-O-acetyl-betulinic acid were mannosylated with tetra-O-benzoyl- or tetra-O-acetyl-alpha-D-mannopyranosyl trichloroacetimidates. De-esterification followed by regioselective dimannosylation of the unprotected monosaccharide derivatives with 2equiv of tetra-O-benzoyl-alpha-D-mannopyranosyl trichloroacetimidate selectively yielded O-3,O-6-linked trimannosides. The cytotoxic activity of selected lupane-type saponins (derivatives of lupeol, betulinic acid, and betulin) toward normal human fibroblasts and various cancer cell lines was also compared.
Cmoch
Piotr
P
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, PL-01-224 Warszawa, Poland.
Pakulski
Zbigniew
Z
Swaczynová
Jana
J
Strnad
Miroslav
M
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008358:Mannose / Q000737:chemistry*; D008362:Mannosides / Q000737:chemistry*; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D053978:Pentacyclic Triterpenes; D012503:Saponins / Q000138:chemical synthesis* / Q000494:pharmacology; D014315:Triterpenes / Q000737:chemistry*; D000094062:Betulinic Acid; D000094042:Lupanes
D000970:Antineoplastic Agents; D008358:Mannose; D008362:Mannosides; D053978:Pentacyclic Triterpenes; D012503:Saponins; D014315:Triterpenes; D000094062:Betulinic Acid; C002503:betulin; C010480:lupeol; D000094042:Lupanes