Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506.
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.
Ohkubo
M
M
Banyu Tsukuba Research Institute, Ibaraki, Japan.
Kojiri
K
K
Kondo
H
H
Tanaka
S
S
Kawamoto
H
H
Nishimura
T
T
Nishimura
I
I
Yoshinari
T
T
Arakawa
H
H
Suda
H
H
Morishima
H
H
Nishimura
S
S
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
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