Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine.

Abstract

A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2'-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2' -amino group with carbamate > amide > urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2'-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2'-(4″-pentynoylamino) 2'-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol.

• Authors: You-Yu Lin, She-Hung Chan, Yu-Pu Juang, Hsin-Min Hsiao, Jih-Hwa Guh, Pi-Hui Liang
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 143 Pg. 1942-1958 (Jan 01 2018) ISSN: 1768-3254 [Electronic] France
• PMID: 29133061 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Saponins
• Oleanolic Acid
• Glucosamine

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Dose-Response Relationship, Drug
• Drug Design
• Drug Screening Assays, Antitumor
• Glucosamine (chemistry, pharmacology)
• Humans
• Molecular Structure
• Oleanolic Acid (chemistry, pharmacology)
• Saponins (chemistry, pharmacology)
• Structure-Activity Relationship
• Tumor Cells, Cultured