title: 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.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Vermont, Burlington 05405.
authors.forename: A P
authors.initials: AP
authors.lastname: Krapcho
authors.forename: M E
authors.initials: ME
authors.lastname: Petry
authors.forename: Z
authors.initials: Z
authors.lastname: Getahun
authors.forename: J J
authors.initials: JJ
authors.lastname: Landi
authors.forename: J
authors.initials: J
authors.lastname: Stallman
authors.forename: J F
authors.initials: JF
authors.lastname: Polsenberg
authors.forename: C E
authors.initials: CE
authors.lastname: Gallagher
authors.forename: M J
authors.initials: MJ
authors.lastname: Maresch
authors.forename: M P
authors.initials: MP
authors.lastname: Hacker
authors.forename: F C
authors.initials: FC
authors.lastname: Giuliani
mesh_terms: 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*
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D007546:Isoquinolines; D008942:Mitoxantrone; C086548:pixantrone; C020182:ametantrone