Synthesis and biological activities of topoisomerase I inhibitors, 6-N-amino analogues of NB-506.

作者信息

Ohkubo M, Kojiri K, Kondo H, Tanaka S, Kawamoto H, Nishimura T, Nishimura I, Yoshinari T, Arakawa H, Suda H, Morishima H, Nishimura S

机构信息

Banyu Tsukuba Research Institute, Ibaraki, Japan.

出版信息

Bioorg Med Chem Lett. 1999 May 3;9(9):1219-24. doi: 10.1016/s0960-894x(99)00188-2.

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.