Cytotoxic activity of N1- and N8-aziridinyl analogs of spermidine

Two isomeric aziridine-containing analogs of spermidine, a polyamine, were synthesized and evaluated for cytotoxic activity against cancer cell lines. Replacement of one of the primary amino groups of spermidine with an aziridinyl functionality yielded either N1-aziridinylspermidine [N-(3-aziridinylpropyl)-1,4-diaminobutane] or N8-aziridinylspermidine [N-(4-aziridinylbutyl)-1,3-diaminopropane]. N1-Aziridinylspermidine was cytotoxic in vitro against L1210 murine leukemia cells (IC50 0.15 microM) and HL60 human leukemia cells (IC50 0.11 microM). N8-Aziridinylspermidine was slightly less potent against L1210 (IC50 0.31 microM) and HL60 (IC50 0.30 microM) cells. When screened by the Developmental Therapeutics Program of the National Cancer Institute, these compounds proved cytotoxic against a wide variety of tumor types. Both compounds inhibited incorporation of radiolabeled thymidine, uridine, and valine into tricholoracetic acid-precipitable material by L1210 cells. Aminoguanidine did not affect the potency of the aziridinylspermidines.