A comparison of chloroambucil- and xylene-containing polyamines leads to improved ligands for accessing the polyamine transport system

    Authors

    N. Kaur; J. G. Delcros; J. Imran; A. Khaled; M. Chehtane; N. Tschammer; B. Martin;O. Phanstiel

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    CHLORAMBUCIL-SPERMIDINE CONJUGATE; BIOLOGICAL EVALUATION; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; SELECTIVE DELIVERY; FLUORESCENT-PROBE; ESCHERICHIA-COLI; ANALOGS; DNA; CYTOTOXICITY; Chemistry, Medicinal

    Abstract

    Several disubstituted arylene- and chloroambucil-polyamine conjugates were synthesized and evaluated for their ability to target cells via their polyamine transport system (PAT). As compared to the monosubstituted analogues, the disubstituted arylene systems were superior PAT targeting agents. Using a Chinese hamster ovary (CHO) cell line (PAT active) and its CHO-MG mutant (PAT inactive), the series was screened for their PAT targeting ability. The data were expressed as a CHOMG/CHO IC(50) ratio. Indeed, the disubstituted systems gave high IC(50) ratios (e.g., ratio > 2000), which indicated high selectivity for the PAT. The chloroambucil adducts were less toxic than the corresponding arylmethyl compounds. In this regard, having the proper recognition element (i.e., homospermidine) and cytotoxic "cargo" were deemed paramount for successful drug delivery via the PAT.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    51

    Issue/Number

    5

    Publication Date

    1-1-2008

    Document Type

    Article

    Language

    English

    First Page

    1393

    Last Page

    1401

    WOS Identifier

    WOS:000253784900031

    ISSN

    0022-2623

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