title: New cytotoxic 19-norbufadienolide and bufogargarizin isolated from Chan Su.
abstract: One new 19-norbufadienolide (1) and one new bufogargarizin (2), together with twelve known bufadienolides (3-14, resp.) were isolated from Chan Su, a traditional Chinese medicine that is used in the treatment of cancer. Their structures were elucidated on the basis of detailed spectroscopic analysis and comparison of corresponding data that is previously reported. The cytotoxic activities of the isolated compounds were evaluated on HeLa and A549 cell lines. Though 1 and 2 showed weak cytotoxic activities on both cell lines, compounds 4 and 5 showed lower IC50 values than bufalin, the most widely studied bufadienolide in Chan Su. Furthermore, four 3-ester derivatives (15-18) of compound 4 were synthesized and their cytotoxic activities were also evaluated. Analysis of the structure-activity relationship indicated that bufadienolides with aldehyde group at C-10 or α-hydroxyl group at C-11 exhibit stronger cytotoxic activities on both cell lines. The cytotoxic activity of arenobufagin-3-ester derivative 17 was 4-fold higher than compound 4.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Meng
authors.affiliation: Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: De-An
authors.initials: DA
authors.lastname: Guo
authors.affiliation: Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China. Electronic address: liujunhua2014@simm.ac.cn.
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, PR China; Shanghai Research Center for the Modernization of Traditional Chinese Medicine, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, PR China. Electronic address: lhhu@simm.ac.cn.
authors.forename: Li-Hong
authors.initials: LH
authors.lastname: Hu
mesh_terms: D000818:Animals; D002018:Bufanolides / Q000737:chemistry* / Q000302:isolation & purification; D002025:Bufonidae; D045744:Cell Line, Tumor / Q000187:drug effects; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008516:Medicine, Chinese Traditional; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C000601742:19-norbufadienolide; D002018:Bufanolides; C000601743:bufogargarizin C; C095591:chan su
keywords: Bufadienolide; Bufo gargarizans Cantor; Cytotoxicity; Toad venom