Divergent activity of derivatives of amsacrine (m-AMSA) towards Lewis lung carcinoma and P388 leukaemia in mice

Abstract

A series of acridine monosubstituted derivatives of the antitumour agent amsacrine [4'-(9-acridinylamino)methanesulphon-m-anisidide] has been tested for activity against intraperitoneally inoculated P388 leukaemia and intravenously inoculated Lewis lung carcinoma growing in DBA/2J X C57BL/6J mice, and treated using a q4d X 3 intraperitoneal injection schedule. Whereas all derivatives tested exhibited moderate to high activity towards the leukaemia, activity against the lung tumour varied from inactive to curative. Amsacrine itself displayed low but statistically significant activity. Cyclophosphamide and 2-beta-D-ribofuranosylthiazole-4-carboxamide (tiazofurin) were highly active. 5-Fluorouracil was active but doxorubicin, daunorubicin, ametantrone and mitoxantrone showed no significant activity. Since the Lewis lung carcinoma is responsive to a high proportion of agents active against solid tumours in the clinic, it is concluded that some derivatives of amsacrine could be considerably more active than amsacrine itself against human solid tumours.