title: Acylated mono-, bis- and tris- cinchona-based amines containing ferrocene or organic residues: synthesis, structure and in vitro antitumor activity on selected human cancer cell lines.
abstract: A series of novel functionalized mono-, bis- and tris-(S)-{[(2S,4R,8R)-8-ethyl-quinuclidin-2-yl](6-methoxyquinolin-4-yl)}methanamines including ferrocene-containing derivatives was obtained by the reaction of the precursor amine with a variety of acylation agents. Their in vitro antitumor activity was investigated against human leukemia (HL-60), human neuroblastoma (SH-SY5Y), human hepatoma (HepG2) and human breast cancer (MCF-7) cells by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay and the 50% inhibitory concentration (IC(50)) values were determined. Our data indicate that the precursor amine has no antitumor activity in vitro, but the bis-methanamines with ureido-, thioureido and amide-type linkers display attractive in vitro cytotoxicity and cytostatic effects on HL-60, HepG2, MCF-7 and SH-SY5Y cells. Besides 1H- and 13C-NMR methods the structures of the new model compounds were also studied by DFT calculations.
authors.affiliation: Institute of Chemistry, Eötvös Loránd University, P. O. B. 32, H-1518 Budapest-112, Hungary. karolbim@caesar.elte.hu
authors.forename: Benedek Imre
authors.initials: BI
authors.lastname: Károlyi
authors.forename: Szilvia
authors.initials: S
authors.lastname: Bösze
authors.forename: Erika
authors.initials: E
authors.lastname: Orbán
authors.forename: Pál
authors.initials: P
authors.lastname: Sohár
authors.forename: László
authors.initials: L
authors.lastname: Drahos
authors.forename: Emese
authors.initials: E
authors.lastname: Gál
authors.forename: Antal
authors.initials: A
authors.lastname: Csámpai
mesh_terms: D000215:Acylation; D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003198:Computer Simulation; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D000075163:Metallocenes; D008956:Models, Chemical; D008968:Molecular Conformation; D011803:Quinine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; D011803:Quinine; C004998:ferrocene