Abstract
Starting from commercial available natural product oridonin (1), a practical synthesis of ent-6,7-seco-oridonin derivatives (2, 3, 5, and 9) was accomplished and their biological activities were evaluated. The conversion of spirolactone-type diterpenoid to enmein-type was first completed. The results demonstrated that all synthesized ent-6,7-seco-oridonin derivatives could markedly inhibit the proliferation of cancer cells. Compared with Taxol, the most cytotoxic compound 5 has similar potency in A549 cell and slightly less cytotoxicity in Bel-7402 cell. Compound 5 was also more potent than parent compound oridonin in mice with MGC-803 gastric cancer in vivo. Then a series of novel 14-O-derivatives of 5 were further designed and synthesized, which showed better activity than 5 and similar activity as Taxol in vitro. The structure-activity relationships of oridonin derivatives were also discussed in the present investigations.
| Original language | English |
|---|---|
| Pages (from-to) | 242-250 |
| Number of pages | 9 |
| Journal | European Journal of Medicinal Chemistry |
| Volume | 52 |
| DOIs | |
| State | Published - Jun 2012 |
Bibliographical note
Funding Information:This study was supported by grant from National Natural Science Fund (No. 30973610 ), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20100096110001 ), Project for Research and Innovation of Graduates in Universities of Jiangsu Province (2011, No. 800), the Fundamental Research Funds for the Central Universities ( JKY2011030 ) and Key Fund of Ministry of Education of China (No. 108069 ) for financial assistance.
Funding
This study was supported by grant from National Natural Science Fund (No. 30973610 ), Specialized Research Fund for the Doctoral Program of Higher Education (No. 20100096110001 ), Project for Research and Innovation of Graduates in Universities of Jiangsu Province (2011, No. 800), the Fundamental Research Funds for the Central Universities ( JKY2011030 ) and Key Fund of Ministry of Education of China (No. 108069 ) for financial assistance.
| Funders | Funder number |
|---|---|
| Project for Research and Innovation of Graduates in Universities of Jiangsu Province | 800 |
| National Natural Science Foundation of China (NSFC) | 30973610 |
| Ministry of Education of the People's Republic of China | 108069 |
| Fundamental Research Funds for the Central Universities | JKY2011030 |
| Specialized Research Fund for the Doctoral Program of Higher Education of China | 20100096110001 |
Keywords
- Anti-tumor activity
- Cytotoxicity
- Enmein-type diterpenoid
- Spirolactone-type diterpenoid
- Structure-activity relationship
- ent-6,7-seco-Oridonin derivatives
ASJC Scopus subject areas
- Pharmacology
- Drug Discovery
- Organic Chemistry
