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

• Published in: Bioorganic & medicinal chemistry letters 1999-05, Vol.9 (9), p.1219-1224
• Main Authors: Ohkubo, Mitsuru, Kojiri, Katsuhisa, Kondo, Hisao, Tanaka, Seiichi, Kawamoto, Hiroshi, Nishimura, Teruyuki, Nishimura, Ikuko, Yoshinari, Tomoko, Arakawa, Hiroharu, Suda, Hiroyuki, Morishima, Hajime, Nishimura, Susumu
• Format: Article
• Language: English
• Subjects: Animals; Anticancer agents; Antineoplastic agents; Antineoplastic Agents - chemistry; Biological and medical sciences; Carbazoles - chemistry; DNA Topoisomerases, Type I - chemical synthesis; DNA Topoisomerases, Type I - metabolism; Enzyme Inhibitors - chemistry; General aspects; Glucosides - chemistry; Humans; Indoles - chemical synthesis; Indolocarbazole; Inhibitory Concentration 50; Kinetics; Medical sciences; Mice; Models, Chemical; Neoplasms, Experimental - drug therapy; Pharmacology. Drug treatments; Pyrroles - chemical synthesis; Substituent effects; Topoisomerase; Topoisomerase I Inhibitors; Tumor Cells, Cultured
• ISSN: 0960-894X; 1464-3405
• 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-(β- 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. 6- N-Amino analogue of NB-506 [6- N-formylamino-12,13-dihydro-1,11-dihydroxy-13-(β-D-glucopyranosyl)-5 H-indolo[2,3- a]pyrrolo[3,4- c]carbazole-5,7(6 H)-dione] ( 3b), J-109,404 ( 5t), was found to be a more potent anticancer agent in MKN-45 human stomach cancer cells implanted in mice than NB-506.