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.
Krapcho
A P
AP
Department of Chemistry, University of Vermont, Burlington 05405.
Petry
M E
ME
Getahun
Z
Z
Landi
J J
JJ
Stallman
J
J
Polsenberg
J F
JF
Gallagher
C E
CE
Maresch
M J
MJ
Hacker
M P
MP
Giuliani
F C
FC
D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D000880:Anthraquinones / Q000138:chemical synthesis* / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D003110:Colonic Neoplasms / Q000188:drug therapy; D006801:Humans; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D008942:Mitoxantrone / Q000031:analogs & derivatives / Q000627:therapeutic use; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000880:Anthraquinones; D000970:Antineoplastic Agents; D007546:Isoquinolines; D008942:Mitoxantrone; C086548:pixantrone; C020182:ametantrone