|
|||||
|
|
Library Construction and Biological Evaluation of Enmein‐Type Diterpenoid Analogues as Potential Anticancer Agents |
|
| Authors: | Dr Dahong Li Dr Shengtao Xu Hao Cai Lingling Pei Dr Lei Wang Prof Xiaoming Wu Prof Hequan Yao Prof Jieyun Jiang Yijun Sun Prof Jinyi Xu |
| Affiliation: | 1. Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tongjia St., Nanjing 210009 (China);2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjia St., Nanjing 210009 (China);3. Department of Microbiology, Immunology and Molecular Genetics, University of Kentucky College of Medicine, 800 Rose St., Lexington, KY 40536 (USA);4. Drug Screening Center, Nanjing KeyGen Biotech. Co. Ltd. 439 Changhong Road, Nanjing 210012 (China) |
| Abstract: | A library of promising enmein‐type 14‐O‐diterpenoid derivatives was constructed from a commercially available kaurene‐type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel‐7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC‐803 mice). These results warrant further preclinical investigations of these diterpenoid‐based analogues as potential novel anticancer chemotherapeutics. |
| Keywords: | antitumor agents apoptosis cell cycle enmein‐type diterpenoids oridonin |