title: Synthesis, antiproliferative activity and genotoxicity of novel anthracene-containing aminophosphonates and a new anthracene-derived Schiff base.
abstract: A new Schiff base, 9-anthrylidene-furfurylamine and three novel anthracene-containing α-aminophosphonates, [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine, [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were synthesized. The compounds have been characterized by elemental analysis, TLC, IR, NMR and fluorescent spectra. The aminophosphonates and their synthetic precursors were tested for in vitro antitumor activity on a panel of seven human epithelial cancer cell lines. Safety testing was performed both in vitro (3T3 NRU test) and in vivo on ICR mice for genotoxicity and antiproliferative activity. 9-Anthrylidene-furfurylamine and [N-methyl(diethoxyphosphonyl)-1-(9-anthryl)]furfurylamine were most potent cytotoxic agents towards colon carcinoma cell line HT-29. The latter compound exhibited also antiproliferative activity to HBL-100, MDA-MB-231 and 647-V cells. The aminophosphonate [N-methyl(dimethoxyphosphonyl)-1-(9-anthryl)]-p-toluidine and its synthetic precursor 9-anthrylidene-p-toluidine were found to be cytotoxic to HBL-100 and HT-29 tumor cell lines, respectively. Moderate genotoxic and antiproliferative activity in vivo and low toxicity to Balb/c 3T3 (clone 31) mouse embryo cells were observed for all tested compounds. The subcellular distribution of two tested compounds in a tumor cell culture system was also studied.
authors.affiliation: Institute of Polymers, Bulgarian Academy of Sciences, Acad. G. Bonchev Str., Bl. 103A, 1113 Sofia, Bulgaria. kraicheva@yahoo.com
authors.forename: I
authors.initials: I
authors.lastname: Kraicheva
authors.forename: I
authors.initials: I
authors.lastname: Tsacheva
authors.forename: E
authors.initials: E
authors.lastname: Vodenicharova
authors.forename: E
authors.initials: E
authors.lastname: Tashev
authors.forename: T
authors.initials: T
authors.lastname: Tosheva
authors.forename: A
authors.initials: A
authors.lastname: Kril
authors.forename: M
authors.initials: M
authors.lastname: Topashka-Ancheva
authors.forename: I
authors.initials: I
authors.lastname: Iliev
authors.forename: Ts
authors.initials: Ts
authors.lastname: Gerasimova
authors.forename: K
authors.initials: K
authors.lastname: Troev
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000473:pathology; D063065:Organophosphonates / Q000737:chemistry*; D012545:Schiff Bases / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000873:Anthracenes; D000970:Antineoplastic Agents; D063065:Organophosphonates; D012545:Schiff Bases; C034020:anthracene