Design and synthesis of novel oridonin analogues as potent anticancer agents

Journal of Enzyme Inhibition and Medicinal Chemistry

Zheng-Ai Chen¹  Chuan-Feng Liu²  Zhe-Shan Quan²  Hong-Jian Zhang²  Qing-Kun Shen²  Jia-Li Li²  Guo-Hua Gong³ 

[1] Department of Pharmacology, Medical School of Yanbian University, Yanji, China;Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji, China;Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, China;Inner Mongolia Autonomous Region Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Chin;

关键词: Oridonin;    synthesis;    anticancer;    apoptosis;   

DOI  :  10.1080/14756366.2017.1419219

来源: publisher

【 摘 要 】

To identify anticancer agents with higher potency and lower toxicity, a series of oridonin derivatives with substituted benzene moieties at the C17 position were designed, synthesised, and evaluated for their antiproliferative properties. Most of the derivatives exhibited antiproliferative effects against AGS, MGC803, Bel7402, HCT116, A549, and HeLa cells. Compound 2p (IC50 = 1.05 µM) exhibited the most potent antiproliferative activity against HCT116 cells; it was more potent than oridonin (IC50 = 6.84 µM) and 5-fluorouracil (5-FU) (IC50 = 24.80 µM). The IC50 value of 2p in L02 cells was 6.5-fold higher than that in HCT116 cells. Overall, it exhibited better selective antiproliferative activity and specificity than oridonin and 5-FU. Furthermore, compound 2p arrested HCT116 cells at the G2 phase of the cell cycle and increased the percentage of apoptotic cells to a greater extent than oridonin.

【 授权许可】

CC BY