Synthesis and antitumor activity of novel indole podophyllotoxin derivatives.
10.19540/j.cnki.cjcmm.20190321.207
- Author:
Dan-Li TIAN
1
;
Chun-Po LIANG
2
;
Jing LIANG
3
;
Hong CHEN
4
Author Information
1. Tianjin First Center Hospital Tianjin 300192,China.
2. General Hospital of Tianjin Medical University Tianjin 300052,China.
3. Tianjin Huanghe Hospital Tianjin 300110,China.
4. Pharmacognosy Division,Medical College of Chinese People's Armed Police Force Tianjin 300309,China.
- Publication Type:Journal Article
- Keywords:
antitumor activity;
indole;
podophyllotoxin;
structure-activity relationship
- MeSH:
Antineoplastic Agents;
chemical synthesis;
pharmacology;
Drug Screening Assays, Antitumor;
HeLa Cells;
Humans;
Indoles;
chemical synthesis;
pharmacology;
K562 Cells;
Podophyllotoxin;
chemical synthesis;
pharmacology;
Structure-Activity Relationship
- From:
China Journal of Chinese Materia Medica
2019;44(12):2532-2537
- CountryChina
- Language:Chinese
-
Abstract:
According to drug design flattening principle,a series of novel indole podophyllotoxin derivatives which were introduced different indole substituents in C-4 position on the basis of podophyllotoxin nucleus were synthesized with the starting material podophyllotoxin and 1 H-indole-5-carboxylic acid. Its anti-tumor activity in vitro was tested in order to screen for high-efficiency and low-toxic compounds. Six target compounds were synthesized,and were confirmed by~1 H-NMR,~(13)C-NMR,HR-ESI-MS and melting point determination analysis. All these target compounds were not reported by previous literature. Using etoposide as positive control drug,all the target compounds were screened for cytotoxicity against He La cells,K562 cells and K562/A02 cell in vitro by MTT method. The antitumor activity screening results showed that compounds 4 b,4 e,4 f exhibited higher inhibitory rate against He La cells and K562 cells than those of control drug VP-16. This route has the advantages on simple operation and reasonable design,provides some practical reference value for the further development on the structure modification of podophyllotoxin and study on anti-tumor activity.
