Inhibition of in vitro lymphoproliferation by three novel iron chelators of the pyridoxal and salicyl aldehyde hydrazone classes.

The capacity of three novel iron chelators, namely 1-[N-ethoxycarbonylmethylpyridoxylidenium]-2-[2'-pyridyl]hydrazine bromide (EPH), 1-[5'-bromosalicylidene]-2-[2"-pyridyl]hydrazine (BsPH), and 1-pyridoxylidene-2-[1'-phthalazyl]hydrazine dihydrochloride (PPhH), to inhibit the proliferation of mitogen-stimulated murine lymph node cells was examined in vitro. All three are of the aryl hydrazone class, the prototype of which is pyridoxal isonicotinoyl hydrazone. The chelators inhibited lymphoproliferation at low micromolar concentrations. EPH and PPhH had an inhibitory capacity comparable to that of desferrioxamine (IC(50): 3 and 2 microM, respectively), whereas BsPH was more potent (IC(50) < 1 microM). The inhibitory effects of the chelator were not due to cell cytotoxicity and could be abrogated by pretreating the chelator with iron. Time-course studies established a site of action for the chelators at the G(1)/S phase transition. These agents warrant further investigation for their potential as immunosuppressants.