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

Authors Wang R, Li Y, Huai XD, Zheng QX, Wang W, Li HJ, Huai QY

Received 21 February 2018

Accepted for publication 30 March 2018

Published 21 May 2018 Volume 2018:12 Pages 1321—1336

DOI https://doi.org/10.2147/DDDT.S166051

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Colin Mak

Peer reviewer comments 3

Editor who approved publication: Dr Anastasios Lymperopoulos


Rui Wang,1,* Yang Li,2,* Xu-Dong Huai,3 Qing-Xuan Zheng,1 Wei Wang,1 Hui-Jing Li,4 Qi-Yong Huai1

1Marine College, Shandong University, Weihai, China; 2Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital/Affiliated Liaocheng Hospital, Taishan Medical University, Liaocheng, China; 3School of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao, China; 4School of Marine Science and Technology, Harbin Institute of Technology at Weihai, Weihai, China

*These authors contributed equally to this work

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 3m presented the highest inhibitory activities against SGC-7901, MCF-7 and Eca-109 cell lines with IC50 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 IC50 value of 4.11±0.73 µM. Moreover, compound 5b showed the strongest inhibitory activity against Hep-G2 cells with an IC50 value of 3.74±0.18 µM and compound 3l showed strong selective inhibition of the HeLa cells with the lowest IC50 value of 4.32±0.89 µM. A series of pharmacology experiments indicated that compound 5b 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.

Keywords: oleanolic acid, glycyrrhetinic acid, cytotoxic properties, synthesis, apoptosis

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