189341-68-2Relevant academic research and scientific papers
Biologically active spermidine analogues, pharmaceutical compositions and methods of treatment
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, (2008/06/13)
Polyamines having the formula: or a salt thereof with a pharmaceutically acceptable acid wherein: R1-R5may be the same or different and are alkyl, aryl, aryl alkyl, cycloalkyl or hydrogen; at least one of R1and R2/su
A comparison of structure-activity relationships between spermidine and spermine analogue antineoplastics
Bergeron, Raymond J.,Feng, Yang,Weimar, William R.,McManis, James S.,Dimova, Hristina,Porter, Carl,Raisler, Brian,Phanstiel, Otto
, p. 1475 - 1494 (2007/10/03)
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(α),N(ω)- substituents. It appears that there is an optimum chain length for various activities and that the larger the N(α)N(ω)-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.
