title: Synthesis of substituted indeno[1,2-b]quinoline-6-carboxamides, [1]benzothieno[3,2-b]quinoline-4-carboxamides and 10H-quindoline-4-carboxamides: evaluation of structure-activity relationships for cytotoxicity.
abstract: New substituted indeno[1,2-b]quinoline-6-carboxamides, [1]benzothieno[3,2-b]quinoline-4-carboxamides and 10H-quindoline-4-carboxamides were prepared from methyl 2-amino-3-formylbenzoate by a new Friedlander synthesis. Evaluation of these carboxamides for cytotoxicity in a panel of cell lines showed that small lipophilic substituents in the non-carboxamide ring, in a pseudo-peri position to the side chain, significantly increased cytotoxic potency while retaining a pattern of cytotoxicity consistent with a non-topo II mode of action. The methyl-substituted indeno[1,2-b]quinoline-6-carboxamide demonstrated substantial effectiveness (20-day growth delays) in a sub-cutaneous colon 38 in vivo tumor model. This is comparable to that reported for the dual topo I/II inhibitor DACA that is in clinical trial.
authors.affiliation: Chemistry Department, La Trobe University, Bundoora, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: L W
authors.initials: LW
authors.lastname: Deady
authors.forename: J
authors.initials: J
authors.lastname: Desneves
authors.forename: A J
authors.initials: AJ
authors.lastname: Kaye
authors.forename: G J
authors.initials: GJ
authors.lastname: Finlay
authors.forename: B C
authors.initials: BC
authors.lastname: Baguley
authors.forename: W A
authors.initials: WA
authors.lastname: Denny
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003110:Colonic Neoplasms / Q000188:drug therapy; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D007192:Indenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D007192:Indenes; D007211:Indoles; D011804:Quinolines; D013876:Thiophenes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors