Design and Testing of Novel Cytotoxic Polyamine Analogues

Hirak S. Basu, Laurence J. Marton, Malgorzata Pellarin, Dennis F. Deen, James S. McManis, Charles Z. Liu, Raymond J. Bergeron, Burt G. Feuerstein

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


We designed three polyamine analogues, 1,14-diamino-N5-methyl-5,10-diazatetradecane (5me-4-4-4), 1,14-diamino-N5,N5-dimethyl-5,10-diaza-tetradecane (Q-Amm-4-4-4), and 1,14-bis-(ethylamino)-N5,N5-dimethyl-5,10-diazatetradecane (BE-Q-Amm-4-4-4), on the basis of computer modeling and physical-chemical studies of polyamine-DNA interactions. These analogues differ from natural polyamines and from one another in the charge distribution on their aliphatic backbone. We found that 10 μm 5me-4-4-4 did not inhibit growth and was not cytotoxic to the human brain tumor cell lines SF-767 and SF-126. The same concentrations of Q-Amm-4-4-4 and BE-Q-Amm-4-4-4 inhibited cell growth and killed more than 90% of each cell type on day 7 of the experiment BE-Q-Amm-4-4-4 was slightly more toxic than Q-Amm-4-4-4 in both cell lines. All three agents either decreased or completely depleted intracellular putres-cine and spermidine. Q-Amm-4-4-4 and BE-Q-Amm-4-4-4 each also lowered spermine. The fact that 5me-4-4-4 was nontoxic but that Q-Amm-4-4-4 was cytotoxic and inhibited growth suggests that the charge distribution along the surface of the aliphatic backbone of polyamines is important in determining growth inhibition and cytotoxicity.

Original languageEnglish (US)
Pages (from-to)6210-6214
Number of pages5
JournalCancer Research
Issue number23
StatePublished - Dec 1994

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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