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A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics.

Abstract：

:A systematic investigation of the impact of spermidine analogues both in vitro and in vivo is described. The study characterizes the effects of these analogues on L1210 cell growth, polyamine pools, ornithine decarboxylase, S-adenosyl-L-methionine decarboxylase, spermidine/spermine N1-acetyltransferase, the maintenance of cellular charge, i.e., cationic equivalence associated with the polyamines and their analogues, and compares their ability to compete with spermidine for transport. The findings clearly demonstrate that the activity of the linear polyamine analogues is highly dependent on the length of the triamines and the size of the N(alpha),N(omega)-substituents. It appears that there is an optimum chain length for various activities and that the larger the N(alpha),N(omega)-alkyls, the less active the compound. Metabolic transformation including N-dealkylation of these compounds is also evaluated. While there is no monotonic relationship between chain length and the ability of the analogue to be metabolized, the dipropyl triamines are clearly more actively catabolized than the corresponding methyl and ethyl systems. A comparison of the triamines with the corresponding tetraamines is made throughout the text regarding both in vitro activity against L1210 cells and in vivo toxicity measurements, suggesting that several triamine analogues may offer therapeutic advantages over the corresponding tetraamines.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Bergeron RJ,Feng Y,Weimar WR,McManis JS,Dimova H,Porter C,Raisler B,Phanstiel O

doi

10.1021/jm960849j

subject

Has Abstract

pub_date

1997-05-09 00:00:00

pages

1475-94

issue

10

eissn

0022-2623

issn

1520-4804

pii

jm960849j

journal_volume

40

pub_type

杂志文章

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