title: Synthesis, cytotoxicity, and haemolytic activity of chacotrioside lupane-type neosaponins and their germanicane-type rearrangement products.
abstract: The concise synthesis, via a stepwise glycosylation approach, of lupeol, betulin and betulinic acid O-glycosides bearing a chacotriosyl moiety at the C-3 position is described. All neosaponins as well as their rearrangement products of the germanicane-type were evaluated in vitro for their anticancer and haemolytic activities. Although betulinic acid and betulin 3beta-O-chacotriosides were neither cytotoxic nor haemolytic, their rearrangement products allobetulin and 28-oxoallobetulin 3beta-O-chacotriosides (9 and 10) exhibited a cytotoxicity profile up to fourfold superior to betulinic acid against human breast (MCF7) and prostate (PC-3) adenocarcinomas cell lines (IC(50)=10-18 microM). One important result was that only chacotriosides featuring non-polar functions at the C-28 position (6, 9 and 10) exerted a haemolytic activity against red blood cells.
authors.affiliation: Laboratoire LASEVE, Chaire de Recherche sur les Agents Anticancéreux d'Origine Naturelle, Université du Québec à Chicoutimi, Chicoutimi, Québec, Canada.
authors.forename: Charles
authors.initials: C
authors.lastname: Gauthier
authors.forename: Jean
authors.initials: J
authors.lastname: Legault
authors.forename: Marianne
authors.initials: M
authors.lastname: Piochon
authors.forename: Serge
authors.initials: S
authors.lastname: Lavoie
authors.forename: Samuel
authors.initials: S
authors.lastname: Tremblay
authors.forename: André
authors.initials: A
authors.lastname: Pichette
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology; D004912:Erythrocytes / Q000166:cytology / Q000187:drug effects; D053878:Hemolytic Agents / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D012503:Saponins / Q000737:chemistry* / Q000494:pharmacology; D012756:Sheep; D014315:Triterpenes / Q000737:chemistry* / Q000494:pharmacology; D014326:Tropanes / Q000737:chemistry / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D000094062:Betulinic Acid
chemical_list: D003603:Cytotoxins; D053878:Hemolytic Agents; D012503:Saponins; D014315:Triterpenes; D014326:Tropanes; C433845:chacotriose; C480546:lupane; D053978:Pentacyclic Triterpenes; C002503:betulin; D000094062:Betulinic Acid