Title

Synthesis and evaluation of unsymmetrical polyamine derivatives as antitumor agents

Authors

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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