| Glucoside Derivatives Of Podophyllotoxin: Synthesis, Physicochemical Properties, And Cytotoxicity | |
Zi, Cheng-Ting1,2; Yang, Liu2; Kong, Qing-Hua2; Li, Hong-Mei2; Yang, Xing-Zhi2; Ding, Zhong-Tao3; Jiang, Zi-Hua4; Hu, Jiang-Miao2 ; Zhou, Jun2
| |
| 通讯作者 | Jiang, Zi-Hua(zjiang@lakeheadu.ca) ; Hu, Jiang-Miao(hujiangmiao@mail.kib.ac.cn) |
| 2019 | |
| 发表期刊 | DRUG DESIGN DEVELOPMENT AND THERAPY
 |
| ISSN | 1177-8881 |
| 卷号 | 13页码:3683-3692 |
| 摘要 | Background: Widespread concern of the side effects and the broad-spectrum anticancer property of podophyllotoxin as an antitumor agent highlight the need for the development of new podophyllotoxin derivatives. Although some per-butyrylated glucosides of podophyllotoxin and 4 beta-triazolyl-podophyllotoxin glycosides show good anticancer activity, the peracetylated/free of podophyllotoxin glucosides and their per-acetylated are not well studied. Methods: A few glucoside derivatives of PPT were synthesized and evaluated for their in vitro cytotoxic activities against five human cancer cell lines, HL-60 (leukemia), SMMC-7721 (hepatoma), A-549 (lung cancer), MCF-7 (breast cancer), and SW480 (colon cancer), as well as the normal human pulmonary epithelial cell line (BEAS-2B). In addition, we investigated the structure-activity relationship and the physicochemical property-anticancer activity relationship of these compounds. Results: Compound 6b shows the highest cytotoxic potency against all five cancer cell lines tested, with IC50 values ranging from 3.27 +/- 0.21 to 11.37 +/- 0.52 mu M. We have also found that 6b displays higher selectivity than the etoposide except in the case of HL-60 cell line. The active compounds possess similar physicochemical properties: MSA > 900, %PSA < 20, ClogP > 2, MW > 700 Da, and RB > 10. Conclusion: We synthesized several glucoside derivatives of PPT and tested their cytotoxicity. Among them, compound 6b showed the highest cytotoxicity. Further studies including selectivity of active compounds have shown that the selectivity indexes of 6b are much greater than the etoposide except in the case of HL-60 cell line. The active compounds possessed similar physicochemical properties. This study indicates that active glucoside analogs of podophyllotoxin have potential as lead compounds for developing novel anticancer agents. |
| 关键词 | podophyllotoxin glucoside synthesis cytotoxicity physicochemical properties |
| DOI | 10.2147/DDDT.S215895 |
| 收录类别 | SCI ; SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000492143900002 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.kib.ac.cn/handle/151853/70943 |
| 专题 | 植物化学与西部植物资源持续利用国家重点实验室 |
| 通讯作者 | Jiang, Zi-Hua; Hu, Jiang-Miao |
| 作者单位 | 1.Yunnan Agr Univ, Coll Sci, Key Lab Pu Er Tea Sci, Minist Educ, Kunming 650201, Yunnan, Peoples R China 2.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, 132 Lanhei Rd, Kunming 650201, Yunnan, Peoples R China 3.Yunnan Univ, Sch Chem Sci & Technol, Key Lab Med Chem Nat Resource, Minist Educ, Kunming 650091, Yunnan, Peoples R China 4.Lakehead Univ, Dept Chem, 955 Oliver Rd, Thunder Bay, ON P7B 5E1, Canada |
| 推荐引用方式 GB/T 7714 | Zi, Cheng-Ting,Yang, Liu,Kong, Qing-Hua,et al. Glucoside Derivatives Of Podophyllotoxin: Synthesis, Physicochemical Properties, And Cytotoxicity[J]. DRUG DESIGN DEVELOPMENT AND THERAPY,2019,13:3683-3692. |
| APA | Zi, Cheng-Ting.,Yang, Liu.,Kong, Qing-Hua.,Li, Hong-Mei.,Yang, Xing-Zhi.,...&Zhou, Jun.(2019).Glucoside Derivatives Of Podophyllotoxin: Synthesis, Physicochemical Properties, And Cytotoxicity.DRUG DESIGN DEVELOPMENT AND THERAPY,13,3683-3692. |
| MLA | Zi, Cheng-Ting,et al."Glucoside Derivatives Of Podophyllotoxin: Synthesis, Physicochemical Properties, And Cytotoxicity".DRUG DESIGN DEVELOPMENT AND THERAPY 13(2019):3683-3692. |
| 条目包含的文件 | 下载所有文件 | |||||
| 文件名称/大小 | 文献类型 | 版本类型 | 开放类型 | 使用许可 | ||
| Zi-2019-Glucoside De（3776KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | 浏览 下载 | |
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。
修改评论