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

Abstract

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 8a (28-N-methoxyaminooleanane-β-d-glucoside) exhibited the most potent antiproliferative activities against HepG2 cells with IC50 values of 2.1 µM. Further pharmacological experiments revealed that compound 8a 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.

NOTCH Signaling in Osteosarcoma

“…Oleanolic acid (OA), a natural triterpenoid compound, has antitumor activity in a variety of tumors [ 116 , 117 , 118 ]. A study found that OA could inhibit NOTCH signaling, resulting in promoting mitochondrial apoptosis and inhibiting proliferation in a dose-dependent manner in osteosarcoma [ 57 ].…”

Progress in Antimelanoma Research of Natural Triterpenoids and Their Derivatives: Mechanisms of Action, Bioavailability Enhancement and Structure Modifications

“…Du et al [118] synthesized new MeON-Glycoside derivatives of OA by neog lation (general structure: compound 29, Table 7). Due to the large number of deriv we chose those with the strongest cytotoxic activity (IC50 < 10 µM), in which modifi were introduced at the C3 carbon: In another study, A375 cells were treated with rhodamine B-conjugated OA In recent years, many studies have focused on its antitumour effect and cyto towards a wide array of cancer cell lines, including melanoma.…”

“…Du et al [118] synthesized new MeON-Glycoside derivatives of OA by neog lation (general structure: compound 29, Table 7). Due to the large number of deriv we chose those with the strongest cytotoxic activity (IC50 < 10 µM), in which modifi were introduced at the C3 carbon: In recent years, many studies have focused on its antitumour effect and cyto towards a wide array of cancer cell lines, including melanoma.…”

“…Du et al [118] synthesized new MeON-Glycoside derivatives of OA by neogl lation (general structure: compound 29, Table 7). Due to the large number of deriv we chose those with the strongest cytotoxic activity (IC50 < 10 µM), in which modifi were introduced at the C3 carbon: In another study, A375 cells were treated with rhodamine B-conjugated OA d tive (RhodOA) (compound 30, Table 7).…”

“…Du et al [118] synthesized new MeON-Glycoside deriv lation (general structure: compound 29, Table 7). Due to the we chose those with the strongest cytotoxic activity (IC50 < 10 were introduced at the C3 carbon: The authors suggest that the presence of certain substituents at C-28, especially -COONa, -CONH2, -CN and -COOBn, enhanced the apoptotic ability, as compared to the free -COOH group at C-28.…”