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

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

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.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry*
  • Carbazoles / chemistry*
  • DNA Topoisomerases, Type I / chemical synthesis*
  • DNA Topoisomerases, Type I / metabolism*
  • Enzyme Inhibitors / chemistry*
  • Glucosides / chemistry*
  • Humans
  • Indoles / chemical synthesis*
  • Inhibitory Concentration 50
  • Kinetics
  • Mice
  • Models, Chemical
  • Neoplasms, Experimental / drug therapy
  • Pyrroles / chemical synthesis*
  • Topoisomerase I Inhibitors*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Carbazoles
  • Enzyme Inhibitors
  • Glucosides
  • Indoles
  • NB 506
  • Pyrroles
  • Topoisomerase I Inhibitors
  • BE 13793C
  • DNA Topoisomerases, Type I