Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities

  • Bioorg Med Chem Lett. 2015 Jun 1;25(11):2421-4. doi: 10.1016/j.bmcl.2015.03.086.
Yan Luo  1 ,  Ke Wang  2 ,  Meng-han Zhang  2 ,  Da-yong Zhang  3 ,  Yang-chang Wu  4 ,  Xiao-ming Wu  2 ,  Wei-yi Hua  2
Affiliations
  • 1. High Magnetic Field Laboratory, Chinese Academy of Sciences, Shu Shan Hu Rd No. 350, Hefei 230031, China.
  • 2. Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
  • 3. Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China. Electronic address: [email protected].
  • 4. Graduate Institute of Pharmaceutical Chemistry, College of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.
PMID: 25913115 DOI: 10.1016/j.bmcl.2015.03.086
Abstract

There are many reports for andrographolide modification regarding antitumor effects. Transformation of the five-membered lactone ring to furan aromatic ring still results in compounds with good cytotoxicity. To determine further the importance of the five-membered lactone ring and to obtain better lead compounds, we transformed the five-membered lactone ring in andrographolide. New types of ent-labdane diterpene derivatives were made, whose cytotoxic activities were measured in vitro. Preliminary SAR was summarized and two compounds, 7 and 26, with good cytotoxic activity were obtained, which have the potential to be developed into new antitumor drugs.

Keywords
Andrographolide; Cytotoxic activity; SAR; ent-Labdane diterpene.