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Synthesis and Antitumor Activity of 17-carboxylic acid M odified A mide D erivatives of 3-hydroxy betulinic acid

Yi Bi, Jin -Y i Xu, Fei Sun, Xiao -M ing Wu, Wen -C ai Y e, Yi -J un Sun, Qing -G uo Meng and Wen -W en Huang

School of pharmacy, Yantai University, Yantai, Shandong 264005, China ;

Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009 , China ;

Center for Drug Discovery, College of Pharmacy, China ; Pharmaceuticcl University, Nanjing, Jiangsu 210009, China ;

Department of Phytochemistry, China ; Pharmaceutical University, Nanjing, Jiangsu 210009, China ;

Drug Screening Center, Nanjing KeyGen Biotech. Co. Ltd., Nanjing, Jiangsu 210012, China.

Abstract: A novel series of 17-carboxylic acid modified amide derivatives of 3-hydroxy betulinic acid (1) were prepared and tested in vitro against five cell lines: A549 (human lung carcinoma), BEL-7402 (human hepatoma), SF-763 (human cerebroma), B16 (mice melanoma) and HL-60 (human leukaemia) . Within this series of compounds, 4a (IC 50=21.08 μ M in SF-763, IC 50=21.63 μ M in HL-60), 4b (IC 50=28.45 μ M in HL-60,IC 50=29.32 μ M in BEL-7402 ) and 6g (IC 50=26.09 μM in BEL-7402, IC 50=22.65 μM in HL-60) have the mo re potent cytotoxic activity than lead compound 1. The preliminary structure-activity relationship analysis of the C-28 amide derivatives is also discussed.

Keywords: 23-hydroxy betulinic acid ; amide derivatives ; structure modification ; antitumor activity ; structure-activity relationship .