Synthesis of MeON-Glycoside Derivatives of Oleanolic Acid by Neoglycosylation and Evaluation of Their Cytotoxicity Against Selected Cancer Cell Lines

• Main Authors: Zhichao Du, Guolong Li, Xiaoyang Zhou, Jian Zhang
• Format: Article
• Language: English
• Published: MDPI AG 2021-02-01
• Series: Molecules
• Subjects: oleanolic acid; neoglycosides; anticancer; antiproliferation; apoptosis
• Online Access: https://www.mdpi.com/1420-3049/26/3/772

A series of C-3 and C-28 MeON-neoglycosides of oleanolic acid were designed and synthesized by neoglycosylation as potential antiproliferative agents. Their cytotoxicity was evaluated in vitro against five human cancer cell lines: human non-small cell lung cancer cell line (A549), human melanoma cell line (A375), human colon cancer cell line (HCT116), human liver carcinoma cell line (HepG2), human breast adenocarcinoma cell line (MCF-7) by the Cell Counting Kit-8 (CCK-8) assay. Most of C-3 and C-28 MeON-neoglycosides of oleanolic acid exhibited notably inhibitory effects against the tested cancer cells and more sensitive to HepG2 cells than 5-Fluorouracil (5-FU). Structure-activities relationship (SAR) analysis revealed that sugar types and the d/l configuration of sugars would significantly affect their antiproliferative activities of neoglycosides. Among them, compound <b>8a</b> (28-<i>N</i>-methoxyaminooleanane-<i>β</i>-d-glucoside) exhibited the most potent antiproliferative activities against HepG2 cells with IC₅₀ values of 2.1 µM. Further pharmacological experiments revealed that compound<b> 8a</b> could cause morphological changes and cell cycle arrest at G0/G1 phase and induce apoptosis in HepG2 cells. These results suggested that neoglycosylation could provide a rapid strategy for the discovery of potential antiproliferative agents and their possible pharmacological mechanisms need more further research.