Design and preparation of derivatives of oleanolic and glycyrrhetinic acids with cytotoxic properties
| Autor: | Qi-Yong Huai, Wei Wang, Qing-Xuan Zheng, Hui-Jing Li, Xudong Huai, Yang Li, Rui Wang |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
glycyrrhetinic acid synthesis Pharmaceutical Science Cell Line HeLa 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship oleanolic acid Drug Discovery Structure–activity relationship Humans Oleanolic acid IC50 Original Research Cell Proliferation Pharmacology Drug Design Development and Therapy biology Dose-Response Relationship Drug Molecular Structure Chemistry Cell growth apoptosis biology.organism_classification Antineoplastic Agents Phytogenic In vitro 030104 developmental biology Biochemistry Cell culture Apoptosis cytotoxic properties Drug Design Drug Screening Assays Antitumor |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | 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±0.73µM. 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 |
| Databáze: | OpenAIRE |
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