6,9-BIS[(AMINOALKYL)AMINO]BENZO[G]ISOQUINOLINE-5,10-DIONES - A NOVEL CLASS OF CHROMOPHORE-MODIFIED ANTITUMOR ANTHRACENE-9,10-DIONES - SYNTHESIS AND ANTITUMOR EVALUATIONS

Synthetic procedures have been developed which lead to the 2-aza congeners 3 and several related N-oxides 4. The analogues 3 exhibited a wide range of in vitro cytotoxicity against L1210 leukemia, the human colon adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/DX cell line. Selected analogues of 3 showed significant P388 antileukemic activity in mice with 3c exhibiting high activity. This activity was also retained in the related N-oxide 4a. These heterocyclic bioisosteric models are representative of the first anthracene-9,10-diones which display antileukemic activity comparable to mitoxantrone.