Synthesis and biological evaluation of dihydromotuporamine derivatives in cells containing active polyamine transporters

    Authors

    N. Kaur; J. G. Delcros; N. Martin;O. Phanstiel

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    RING-CLOSING-METATHESIS; XESTOSPONGIA-EXIGUA KIRKPATRICK; MAMMALIAN-CELLS; MOLECULAR REQUIREMENTS; PROTONATION CONSTANTS; SELECTIVE DELIVERY; NUCLEIC-ACIDS; SPERMIDINE; ANALOGS; MOTUPORAMINES; Chemistry, Medicinal

    Abstract

    Dihydromotuporamine C (4) and its 4,4-triamine analogue (5) were synthesized in good yield using ring-closing metathesis (RCM) methods. Comparison of their biological activities (K-i determinations in L1210 cells and IC50 determinations in L1210, CHO, and CHO-MG cells) revealed that the motuporamine derivatives do not use the polyamine transporter (PAT) for cellular entry. Bioevaluation of a N-1-(anthracen-9-ylmethyl)-N-1-(ethyl)homospermidine control (7) revealed that the presence of a N-1 tertiary amine center imparted a significant reduction in the PAT affinity of the polyamine conjugate and abolished its PAT-targeting selectivity.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    48

    Issue/Number

    11

    Publication Date

    1-1-2005

    Document Type

    Article

    Language

    English

    First Page

    3832

    Last Page

    3839

    WOS Identifier

    WOS:000229443700021

    ISSN

    0022-2623

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