title: Synthesis and in vitro cytotoxic effect of 6-amino-substituted 11H- and 11Me-indolo[3,2-c]quinolines.
abstract: A series of 6-amino-11H- indolo[3,2-c]quinoline derivatives with various substituents on the quinoline ring were synthesized. A methyl group introduced to N-11 of the intermediate 4 to elaborate novel analog 7. The cytotoxic effect of these 6-amino-substituted 11H- and 11-methyl-indolo[3,2-c]quinoline derivatives in vitro were tested against MV4-11 (human leukemia), A549 (non-small cell lung cancer) and HCT116 (colon cancer) and BALB/3T3 (normal murine fibroblasts). All the N-11 methylated compounds significantly increased the cytotoxicity. Compound 7p was most active with the IC50 value of 0.052 μM against the MV4-11 cell line, and also exhibited a selective activity against A549, HCT116 and BALB/3T3 cell line, with the respective IC50 values of 0.112, 0.007 and 0.083 μM, which were higher or comparable to those of the anticancer drug doxorubicin HCl. The binding constants of 5g and 7h to salmon fish sperm DNA were also evaluated using UV-vis absorption spectroscopy, indicating intercalation binding with constants of 1.05 × 10(6) L/mol and 4.84 × 10(6) L/mol.
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Science, 12, R. Weigl Street, 53-114 Wroclaw, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Świtalska
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Ming-Yu
authors.initials: MY
authors.lastname: Wu
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Imai
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Tran Anh
authors.initials: TA
authors.lastname: Ngoc
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Cui-Qing
authors.initials: CQ
authors.lastname: Pang
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Immunology and Experimental Therapy, Polish Academy of Science, 12, R. Weigl Street, 53-114 Wroclaw, Poland. Electronic address: wietrzyk@iitd.pan.wroc.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.affiliation: Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: inokuchi@cc.okayama-u.ac.jp.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Inokuchi
mesh_terms: D000818:Animals; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects*; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D011804:Quinolines
keywords: 11-H-indolo[3,2-c]quinoline; 11-Methyl-indolo[3,2-c]quinoline; Anticancer agents; Cytotoxicity; Isocryptolepine congener