Looking for optimised analogues of compound 2 that might be useful in colon cancer therapy, we here explore the in vitro cytotoxicity against MDA-MB 231 human breast carcinoma, A-549 human lung carcinoma and HT-29 human colon carcinoma cell lines of several analogues and derivatives. The effect of the R2-substituent and/or the introduction of an arylmethyl side-chain at C-3, as well as the presence of a double bond in the skeleton or a methoxy group at C-1 have been investigated. New 6,15-iminoisoquino[3,2-b]3-benzazocine compounds, related to the saframycin family, in which the C(7)-N(8)-C(9)-substructure contains a lactam function, a fused oxazolidine or an aminonitrile function were also studied, and many of them showed low micromolar GI50 values.