Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties.

BACKGROUND

The structural modification of natural products with the aim to improve the anticancer activity is a popular current research direction. The pentacyclic triterpenoid compounds oleanolic acid (OA) and glycyrrhetinic acid (GA) are distributed widely in nature.

METHODS

In this study, various oleanolic acids and glycyrrhetinic acids were designed and synthesized by using the combination principle. The in vitro anticancer activities of new OA and GA derivatives were tested by the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) method with SGC-7901 (gastric cancer), MCF-7 (breast cancer), Eca-109 (esophageal cancer), HeLa (cervical cancer), Hep-G2 (hepatoma cancer) and HSF (normal human skin fibroblast) cells.

RESULTS AND CONCLUSION

The screening results showed that the compound presented the highest inhibitory activities against SGC-7901, MCF-7 and Eca-109 cell lines with IC values of 7.57±0.64 μM, 5.51±0.41 μM and 5.03±0.56 μM, respectively. In addition, this compound also showed effective inhibition of Hep-G2 cells with an IC value of 4.11±0.73 μM. Moreover, compound showed the strongest inhibitory activity against Hep-G2 cells with an IC value of 3.74±0.18 μM and compound showed strong selective inhibition of the HeLa cells with the lowest IC value of 4.32±0.89 μM. A series of pharmacology experiments indicated that compound could induce Hep-G2 cells autophagy and apoptosis. These compounds will expand the structural diversity of anti-cancer targets and confirm the prospects for further research.