The effect of 12-alkoxy modification on the in vitro antileukaemic activity of N-methyl 2,3,8,9-tetramethoxybenzo[c]phenanthridinium salts.

Abstract

Some members of a series of 12-alkyloxy benzo[c]phenanthridines are potent inhibitors of the growth of P388 tumour cells in vitro, with a strong dependence on the nature of the 12-substituent. Analogues with a quaternary nitrogen in the side chain bind strongly to DNA but are less active against the tumour cells. The multi-drug-resistant cell line Pr8/22 shows less sensitivity to the new compounds. K562 Human leukaemia cells undergo differentiation in the presence of the benzo[c]phenanthridine derivatives with a structure-activity relationship which does not correlate well with potency against the P388 cell line.