Synthesis of new ent-labdane diterpene derivatives from andrographolide and evaluation on cytotoxic activities.
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.
High Magnetic Field Laboratory, Chinese Academy of Sciences, Shu Shan Hu Rd No. 350, Hefei 230031, China.
Yan
Y
Luo
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
Ke
K
Wang
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
Meng-han
MH
Zhang
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China. Electronic address: zhangdayong@cpu.edu.cn.
Da-yong
DY
Zhang
Graduate Institute of Pharmaceutical Chemistry, College of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan.
Yang-chang
YC
Wu
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
Xiao-ming
XM
Wu
Center of Drug Discovery & State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24, Tongjia Xiang, Nanjing 210009, China.
Wei-yi
WY
Hua
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D055808:Drug Discovery; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D004224:Diterpenes; C030419:andrographolide
Andrographolide; Cytotoxic activity; SAR; ent-Labdane diterpene