Novel indolocarbazole compound 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 (NB-506): its potent antitumor activities in mice.

Abstract

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)-di one d is a new antitumor indolocarbazole compound. The growths of murine M5076 and Ehrlich solid tumors were inhibited 76 and 96%, respectively, by i.v. injection at doses of 300 mg/m2. Furthermore, NB-506 caused regression of nodules of human PC-13 lung cancer and MKN-45 stomach cancer cells at i.v. doses of 90 mg/m2. Human HCT 116 and LS 180 colon cancers also regressed with injections of NB-506. Repeated injections of NB-506 had a stronger antitumor effect than intermittent injections in mice with MKN-45. The cumulative toxicity of NB-506 was low in terms of lethality in mice, i.e., the LD50s on single and 10 repeated i.v. injections into CDF1 mice were 990 and 810 mg/m2/injection, respectively. In conclusion, NB-506 is considered to be an interesting possible candidate as an anticancer drug for treatment of solid tumors in humans.