ABSTRACT
N-Acetylglucosamine-bearing triterpenoid saponins (GNTS) were reported to be a unique type of saponins with potent anti-tumor activity. In order to study the structure-activity relationship of GNTS, 24 oleanolic acid saponins with (1 --> 3)-linked, (1 --> 4)-linked, (1 --> 6)-linked N-acetylglucosamine oligosaccharide residues were synthesized in a combinatorial and concise method. The cytotoxicity of these compounds toward the leukemia cell line HL-60 and the colorectal cancer cell line HT-29 could not be improved. Half maximal inhibition below 10 µM was achieved in one single case. The study revealed that the activity decreased following the order of 3' > 4' > 6' glycosyl modifications. GNTS that incorporated (D/L)-xylose and L-arabinose at positions 3' and 4' were more potent than those bearing other sugars.
Subject(s)
Acetylglucosamine/chemistry , Acetylglucosamine/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Oleanolic Acid/chemistry , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Acetylglucosamine/chemical synthesis , Antineoplastic Agents/chemical synthesis , Chemistry Techniques, Synthetic , Combinatorial Chemistry Techniques , Glycosylation , HL-60 Cells , HT29 Cells , Humans , Small Molecule Libraries/chemical synthesis , Structure-Activity RelationshipABSTRACT
Naturally occurring spirostanol saponins bear a chacotriose, α-L-rhamnopyranosyl-(1â2)-[α-L-rhamnopyranosyl-(1â4)]-ß-D-glucopyranose residue as the oligosaccharide moiety which is believed to be important for biological activity. Herein the development of a concise, combinatorial method for the synthesis of two series of glycan variants at the 2' and/or 4' positions of chacotriose is described and the structure-activity relationships of the glycone part at 3-OH of chlorogenin investigated. These compounds were found to be weakly-cytotoxic toward leukemia cell lines CCRF and HL-20, indicating that the chacotriose moiety is important for anticancer activity.