Synthesis, cytotoxicity, and haemolytic activity of chacotrioside lupane-type neosaponins and their germanicane-type rearrangement products.
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.
Gauthier
Charles
C
Laboratoire LASEVE, Chaire de Recherche sur les Agents Anticancéreux d'Origine Naturelle, Université du Québec à Chicoutimi, Chicoutimi, Québec, Canada.
Legault
Jean
J
Piochon
Marianne
M
Lavoie
Serge
S
Tremblay
Samuel
S
Pichette
André
A
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
D003603:Cytotoxins; D053878:Hemolytic Agents; D012503:Saponins; D014315:Triterpenes; D014326:Tropanes; C433845:chacotriose; C480546:lupane; D053978:Pentacyclic Triterpenes; C002503:betulin; D000094062:Betulinic Acid