Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties
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, Liaochen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-05-01
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| Series: | Drug Design, Development and Therapy |
| Subjects: | |
| Online Access: | https://www.dovepress.com/design-and-preparation-of-derivatives-of-oleanolic-and-glycyrrhetinic--peer-reviewed-article-DDDT |
| _version_ | 1818518894465253376 |
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| author | Wang R Li Y Huai XD Zheng QX Wang W Li HJ Huai QY |
| author_facet | Wang R Li Y Huai XD Zheng QX Wang W Li HJ Huai QY |
| author_sort | Wang R |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-11T01:16:29Z |
| format | Article |
| id | doaj.art-310dda73075249e0a1d136e523595ce3 |
| institution | Directory Open Access Journal |
| issn | 1177-8881 |
| language | English |
| last_indexed | 2024-12-11T01:16:29Z |
| publishDate | 2018-05-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Drug Design, Development and Therapy |
| spelling | doaj.art-310dda73075249e0a1d136e523595ce32022-12-22T01:25:51ZengDove Medical PressDrug Design, Development and Therapy1177-88812018-05-01Volume 121321133638421Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic propertiesWang RLi YHuai XDZheng QXWang WLi HJHuai QYRui 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, apoptosishttps://www.dovepress.com/design-and-preparation-of-derivatives-of-oleanolic-and-glycyrrhetinic--peer-reviewed-article-DDDToleanolic acidglycyrrhetinic acidcytotoxic propertiessynthesisapoptosis |
| spellingShingle | Wang R Li Y Huai XD Zheng QX Wang W Li HJ Huai QY Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties Drug Design, Development and Therapy oleanolic acid glycyrrhetinic acid cytotoxic properties synthesis apoptosis |
| title | Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| title_full | Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| title_fullStr | Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| title_full_unstemmed | Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| title_short | Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| title_sort | design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties |
| topic | oleanolic acid glycyrrhetinic acid cytotoxic properties synthesis apoptosis |
| url | https://www.dovepress.com/design-and-preparation-of-derivatives-of-oleanolic-and-glycyrrhetinic--peer-reviewed-article-DDDT |
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