title: New pyridocarbazole derivatives. Synthesis and their in vitro anticancer activity.
abstract: In this paper, we describe our results of the synthesis and biological testing of analogues of the natural alkaloids olivacine and ellipticine. We have synthesized fourteen new 1-substituted pyrido[4,3-b]carbazole derivatives. All of them were tested in vitro for their anticancer activity on three human tumor cell lines: CCRF/CEM (T lymphoblast leukemia), A549 (lung adenocarcinoma), and MCF7 (breast cancer). Cytotoxicity to non-cancer cells was estimated in cultures of the mice fibroblast cell line 3T3 BALB. The anticancer activity of 9-methoxy-5,6-dimethyl-1-[(1,1-bis-hydroxymethyI-propylamino)-methyl]-6H-pyrido[4,3-b]carbazole (compound 9) was the strongest amongst compounds tested on the three cancer cell lines; it was about 5 times higher than ellipticine and about 10% higher than doxorubicin.
authors.affiliation: Department of Organic Chemistry, Wrocław Medical University, Faculty of Pharmacy, Borowska 211, 50-556 Wrocław, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Jasztold-Howorko
authors.forename: Beata
authors.initials: B
authors.lastname: Tylińska
authors.forename: Bogusława
authors.initials: B
authors.lastname: Biaduń
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gebarowski
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Gasiorowski
mesh_terms: D016475:3T3 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002227:Carbazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002227:Carbazoles; D004611:Ellipticines; D007202:Indicators and Reagents; C034192:ellipticine; C011521:olivacine