Comparison of the structural and cytotoxic activity of novel 2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone analogues

Eight analogues of 2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone have been synthesized and tested for cytotoxicity against four different leukemic and lymphomic cell lines. For K562 and BSM cells, the toxicity could be correlated with the ease of reduction of the compounds as determined by the one-electron reduction potentials and the electron spin resonance detection of the reduced compounds produced by the cells. The cell toxicity could also be correlated with the efficiency of the compounds to form cross-links in DNA. However, no such correlations could be observed for the L1210 and Raji cells, although the activity of the NADPH dependent reducing enzymes in these cells was similar to that in the others. It is believed that for the L1210 and Raji cells, the influx/efflux of the different compounds may be more important to the cytotoxicity than their reduction or alkylation.