title: Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506.
abstract: 6-N-Amino analogues of NB-506 [6-N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(beta-D-glucopyranosyl) -5H-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(6H)-dione] (3b) were synthesized and tested with respect to topoisomerase inhibition, cytotoxicity and anticancer effects. Among them, a 1,3-dihydroxypropane analogue (J-109,404, 5t) showed more than ten times more potent anticancer activity in MKN-45 human stomach cancer cells implanted in mice than NB-506.
authors.affiliation: Banyu Tsukuba Research Institute, Ibaraki, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ohkubo
authors.forename: K
authors.initials: K
authors.lastname: Kojiri
authors.forename: H
authors.initials: H
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Tanaka
authors.forename: H
authors.initials: H
authors.lastname: Kawamoto
authors.forename: T
authors.initials: T
authors.lastname: Nishimura
authors.forename: I
authors.initials: I
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Yoshinari
authors.forename: H
authors.initials: H
authors.lastname: Arakawa
authors.forename: H
authors.initials: H
authors.lastname: Suda
authors.forename: H
authors.initials: H
authors.lastname: Morishima
authors.forename: S
authors.initials: S
authors.lastname: Nishimura
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry*; D002227:Carbazoles / Q000737:chemistry*; D004264:DNA Topoisomerases, Type I / Q000138:chemical synthesis* / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis*; D020128:Inhibitory Concentration 50; D007700:Kinetics; D051379:Mice; D008956:Models, Chemical; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011758:Pyrroles / Q000138:chemical synthesis*; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D005960:Glucosides; D007211:Indoles; C092476:NB 506; D011758:Pyrroles; D059004:Topoisomerase I Inhibitors; C070538:BE 13793C; D004264:DNA Topoisomerases, Type I