title: Human DNA topoisomerase I poisoning activity of bis-1-aminomethylnaphtalenes. A correlation with their cytotoxic activity.
abstract: Symmetrical bis-1-aminmoethylnaphtalenes, a group of compounds that demonstrated cytotoxicity towards human tumor cell lines, showed human topoisomerase I poisoning activity. The compounds tested were: N,N'-bis-1-naphthylmethyl-1,6-hexanediamine (1a), N,N'-bis-1-naphthylmethyl-1,8-octanediamine (1b), N,N'-bis-1-naphthylmethyl-1,12-dodecanediamine (1c), N,N'-bis-1-naphthylmethyl-4,4-bipiperidine (2) and N-(1-naphthylmethyl)-N'-dimethyl-1,3-diaminepropane dichlorhydrate (3). All showed human topoisomerase I inhibition by producing protein-linked DNA breaks. The most active were 1a, 1b, 1c with a percentage stimulation of DNA cleavage of 75, 84 and 70% at 100 micrograms/ml, respectively. Compounds 2 and 3 were moderately active as poisons of topoisomerase I activity, the former showing 58% stimulation of DNA cleavage at 100 micrograms/ml and the latter a 24% stimulation. The correlation observed between topoisomerase I poisoning and in vitro cytotoxic activity suggests that this could be a possible mechanism for the cytotoxicity observed in tumor cell lines.
authors.affiliation: Cátedra de Farmacognosia, IQUIMEFA-CONICET, Universidad de Buenos Aires, Argentina. aromano@huemul.ffyb.uba.ar
authors.forename: A
authors.initials: A
authors.lastname: Romano
authors.forename: E
authors.initials: E
authors.lastname: Mongelli
authors.forename: A M
authors.initials: AM
authors.lastname: Bruno
authors.forename: C
authors.initials: C
authors.lastname: Gaozza
authors.forename: J
authors.initials: J
authors.lastname: Coussio
authors.forename: G
authors.initials: G
authors.lastname: Ciccia
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D004249:DNA Damage; D004278:DNA, Superhelical / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004278:DNA, Superhelical; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D059004:Topoisomerase I Inhibitors