Synthesis and evaluation of unsymmetrical polyamine derivatives as antitumor agents

    Authors

    J. H. Wang; S. Q. Xie; Y. J. Li; Y. J. Guo; Y. F. Ma; J. Zhao; O. Phanstiel;C. J. Wang

    Comments

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    Abbreviated Journal Title

    Bioorg. Med. Chem.

    Keywords

    unsymmetrical polyamine conjugate; synthesis; cytotoxicity; antitumor; BIOLOGICAL EVALUATION; MOLECULAR REQUIREMENTS; SELECTIVE DELIVERY; TOPOISOMERASE-II; MAMMALIAN-CELLS; TRANSPORT; CYTOTOXICITY; ANALOGS; HOMOLOGATION; SPERMIDINE; Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, ; Organic

    Abstract

    A series of unsymmetrically substituted polyamine derivatives were prepared and their cytotoxicities in mouse leukemia L1210, melanoma B16, and HeLa cells were investigated. The in vitro cytotoxicity revealed that these conjugates could recognize the polyamine transporter, and the N-ethyl modified homospermidine moiety may be another efficient carrier as homospermidine even though the introduction of terminal alkyl groups led to reduced cytotoxicity in comparison with the un-substituted counterpart 1. The ornithine decarboxylase and topoisomerase II inhibition experiments indicated that ODC and TOPO II were potential, but not unique targets of these conjugates. Furthermore, the in vivo antitumor activities illustrated that the representative conjugate 2f and the homospermidine analogue 1 evidently inhibited the tumor growth and significantly increased the survival time of mice-bearing sarcoma 180 cells. (c) 2008 Elsevier Ltd. All rights reserved.

    Journal Title

    Bioorganic & Medicinal Chemistry

    Volume

    16

    Issue/Number

    14

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    7005

    Last Page

    7012

    WOS Identifier

    WOS:000257829600038

    ISSN

    0968-0896

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