title: New derivatives of 11-methyl-6-[2-(dimethylamino)ethyl]-6H-indolo[2,3-b]quinoline as cytotoxic DNA topoisomerase II inhibitors.
abstract: Novel indolo[2,3-b]quinoline derivatives substituted at N-6 and C-2 or C-9 positions with (dimethylamino)ethyl chains linked to heteroaromatic core by ether, amide or amine bonds, were manufactured and evaluated in vitro for their cytotoxic activity against several cell lines of different origin including multidrug resistant sublines and tested for their ability to influence the cell cycle and inhibit topoisomerase II activity. It was found, that all compounds show cytotoxic activity against cell lines tested, including multidrug resistant LoVo/DX, MES-SA/DX5 and HL-60 sublines. The tested compounds induce the G(2)M phase cell cycle arrest in Jurkat cells, and inhibit topoisomerase II activity.
authors.affiliation: Pharmaceutical Research Institute, 8 Rydygiera St., Warszawa 01-793, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Luniewski
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Joanna
authors.initials: J
authors.lastname: Godlewska
authors.forename: Marta
authors.initials: M
authors.lastname: Switalska
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Piskozub
authors.forename: Wanda
authors.initials: W
authors.lastname: Peczynska-Czoch
authors.forename: Lukasz
authors.initials: L
authors.lastname: Kaczmarek
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019169:Jurkat Cells / Q000187:drug effects; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C577884:11-methyl-6-(2-(dimethylamino)ethyl)-6H-indolo(2,3-b)quinoline; D000970:Antineoplastic Agents; D007211:Indoles; D011804:Quinolines; D059005:Topoisomerase II Inhibitors; D004250:DNA Topoisomerases, Type II