Antineoplastic and antiherpetic activity of spermidine catecholamide iron chelators.

Abstract

A series of iron chelating agents including the bacterial siderophores, parabactin and bis-N1,N8(2,3 dihydroxybenzoyl )spermidine, and four related compounds were synthesized and tested biologically. They were found: (a) to inhibit growth of cultured L1210 leukemia cells at IC50 values of 2-14 microM, (b) to inhibit replication of the DNA virus, herpes simplex type I, in monkey kidney cells at IC50 values of 0.4 microM ( parabactin ) to 55 microM, and (c) to be inactive against the RNA virus, vesicular stomatitis, at concentrations up to 1 mM. All effects were fully preventable by exogenous Fe (III). The activities correlated generally with the iron formation constants (10(36) to 10(48) moles/1) and more specifically with the lipophilicity of the compounds. The data suggest inhibition of DNA (but not RNA) synthesis by interference with the iron-containing enzyme, ribonucleotide reductase.

• Authors: R J Bergeron, P F Cavanaugh Jr, S J Kline, R G Hughes Jr, G T Elliott, C W Porter
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 121 Issue 3 Pg. 848-54 (Jun 29 1984) ISSN: 0006-291X [Print] United States
• PMID: 6331431 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Antiviral Agents
• Iron Chelating Agents
• Siderophores
• Spermidine

Topics

• Animals
• Antineoplastic Agents
• Antiviral Agents
• Iron Chelating Agents (pharmacology)
• Leukemia L1210 (drug therapy)
• Mice
• Siderophores
• Simplexvirus (drug effects, growth & development)
• Spermidine (analogs & derivatives, pharmacology)
• Virus Replication (drug effects)