PNU 157977: a new potent antitumour agent exhibiting low in vivo toxicity in mice injected with L1210 leukaemia cells

The design, synthesis, in vitro and in vivo activity against L1210 murine l eukaemia of the dibromo nitrogen mustard derivative of 2, called PNU 157977 , is described and the structure-activity relationship discussed. This dibr omo derivative is almost two orders of magnitude more cytotoxic than the di chloro counterpart having the same oligopeptidic chain (IC50 2.7 ng/ml vers us 225 ng/ml), and it showed in who an increased survival time which is 5- and 3-fold longer than that of tallimustine and 2 (and T/C 750 versus 133 a nd 213) respectively. Moreover PNU 157977 shows activity against the M5076 solid tumour markedly inferior to that of the closely analogous 2. Footprin ting experiments conducted using the oestrogen receptor PCR probe as the fo otprinting target molecule show that PNU 157977 possesses a different sewue nce-specific alkylation and greater cleavage activity than either 2 or tall imustine.