Synthesis of dihydrosterculic acid-based monoglucosyl diacylglycerol and its analogues and their biological evaluation

• Lactobacillus plantarum glycolipid, GL1 molecule was synthesized in β-configuration.
• β-configuration of GL1 was assigned by 2D-ROESY (NOE) and J-coupling analysis.
• Dihydrosterculic acid was synthesized by Furukawa's reagent with high yields.
• Compound 7b was promising and inhibited cell proliferation in MCF-7 cells.
• Compound 7b activated caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.

In the present study, Lactobacillus plantarum glycolipid (GL1) molecule in β-configuration and its fatty acid analogues were synthesized using trichloroacetimidate methodology. The β-configuration of the GL1 molecule was unambiguously assigned by NMR studies using 2D-ROESY (NOE) and J-coupling analysis. Dihydrosterculic acid was synthesized using Furukawa's reagent and the selective esterification of dihydrosterculic acid at C-3 position of glycerol was achieved with EDC-HCl at 0 °C. In vitro cytotoxicity of the GL1 molecule and its fatty acid analogues was evaluated against DU145, A549, SKOV3 and MCF7 cell lines. Among all the synthesized molecules, the GL1 molecule and compound 7d showed moderate activity, while the compound 7b showed promising activity against all the tested cell lines with IC50 values of 20.1, 18.2, 19.1 and 17.6 μM, respectively. In addition, all tested compounds showed poor cytotoxicity against normal HUVEC cells. The MCF7 cells when treated with compound 7b showed lower bromodeoxyuridine incorporation levels as compared to untreated cells, suggesting that the compound 7b was highly effective and inhibited the cell proliferation. In addition, the compounds showed significant increase in caspases 3 and 9 levels by inducing apoptosis in MCF 7 cells.

Figure optionsDownload as PowerPoint slide