title: Synthesis and cytotoxicity evaluation of 4'-amino-4'-dehydroxyloleandrin derivatives.
abstract: A series of C4'-substituted oleandrin analogues were designed, synthesized and evaluated for their cytotoxicity towards human cervical carcinoma cell line (HeLa). The structure-activity relationships (SARs) of these compounds were summarized in this paper, and 4'-α-amino-4'-dehydroxyloleandrin 4a (IC50=21.7nM) and 4'-β-amino-4'-dehydroxyloleandrin 4b (IC50=10.9nM) exhibited stronger cytotoxicity compared with oleandrin (IC50=33.3nM). Furthermore, the cytotoxicity of these two compounds towards another five human cancer cell lines (NCI-H266, A549, Jurkat, HL-60 and PC-3) was also evaluated and the IC50 values of β-amino derivative 4b were approximately 2-3 folds lower than that of oleandrin.
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China.
authors.forename: Hu
authors.initials: H
authors.lastname: Chen
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: mlei@simm.ac.cn.
authors.forename: Min
authors.initials: M
authors.lastname: Lei
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Biao
authors.initials: B
authors.lastname: Ma
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Miao
authors.initials: M
authors.lastname: Liu
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China.
authors.forename: Dean
authors.initials: D
authors.lastname: Guo
authors.affiliation: State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: xuanliu@simm.ac.cn.
authors.forename: Xuan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, PR China; State key Laboratory of Drug Research, Shanghai Institute of Materia Medica, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, PR China. Electronic address: lhhu@simm.ac.cn.
authors.forename: Lihong
authors.initials: L
authors.lastname: Hu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry*; D002298:Cardenolides / Q000138:chemical synthesis / Q000737:chemistry*; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: C000613794:4'-alpha-amino-4'-dehydroxyloleandrin 4a; D000970:Antineoplastic Agents; D002298:Cardenolides; C021065:oleandrin
keywords: Antitumor agent; Cytotoxicity; Natural product; Oleandrin; Structure-activity relationships (SARs)