Synthesis and bioevaluation of N-(arylalkyl)-homospermidine conjugates

    Authors

    S. Q. Xie; P. F. Cheng; G. C. Liu; Y. F. Ma; J. Zhao; M. Chehtane; A. R. Khaled; O. Phanstiel;C. J. Wang

    Comments

    Authors: contact us about adding a copy of your work at STARS@ucf.edu

    Abbreviated Journal Title

    Bioorg. Med. Chem. Lett.

    Keywords

    homospermidine; polyamine conjugate; synthesis; apoptosis; ACTIVE POLYAMINE TRANSPORTERS; MOLECULAR REQUIREMENTS; BIOLOGICAL; EVALUATION; SELECTIVE DELIVERY; CANCER CELLS; HOMOLOGATION; DERIVATIVES; ANALOGS; AGENTS; Chemistry, Medicinal; Chemistry, Organic

    Abstract

    N'-(Arylalkyl)homospermidines (Ic-1f) and terminally piperazine-substituted homospermidine conjugates (2a-2e) were synthesized and evaluated for cytotoxicity in mouse leukemia L 1210, alpha-difluorometliylornithine (DFMO)-treated L 12 10, melanoma B 16, spermidine (SPD)-treated B 16, and HeLa cell lines. Results demonstrated that homospermidine was a more effective vector than piperazine-substituted homospermidine in ferrying diverse arenes into cells via the polyamine transporter. The leading compound, 9-anthracenemethyl-homospermidine (1a), was shown to induce apoptosis in B16 cells and IL-3 dependent FL5.12A proB cells. The novel conjugate 4-biphenylmethyl-homospermidine (1e) could also induce apoptosis. However, it exhibited different effect on the cell cycle of B16 cells compared to la. (c) 2007 Elsevier Ltd. All rights reserved.

    Journal Title

    Bioorganic & Medicinal Chemistry Letters

    Volume

    17

    Issue/Number

    16

    Publication Date

    1-1-2007

    Document Type

    Article

    Language

    English

    First Page

    4471

    Last Page

    4475

    WOS Identifier

    WOS:000248877800013

    ISSN

    0960-894X

    Share

    COinS