Synthesis and anti-cancer activity of a glycosyl library of N-acetylglucosamine-bearing oleanolic acid.
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.
School of Pharmacy, College of Medicine, National Taiwan University, 1 Jen-Ai Road, Section 1, Taipei, 100, Taiwan.
Yi-Bing
YB
Zeng
Hsin-Min
HM
Hsiao
She-Hung
SH
Chan
Ying-Hsin
YH
Wang
You-Yu
YY
Lin
Yu-Hsuan
YH
Kuo
Jih-Hwa
JH
Guh
Pi-Hui
PH
Liang
D000117:Acetylglucosamine / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D020650:Combinatorial Chemistry Techniques; D006031:Glycosylation; D018922:HL-60 Cells; D019073:HT29 Cells; D006801:Humans; D009828:Oleanolic Acid / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D054852:Small Molecule Libraries; D009828:Oleanolic Acid; D000117:Acetylglucosamine