Antineoplastic and antiherpetic activity of spermidine catecholamide iron chelators

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.