Syntheses and biological activities of rebeccamycin analogues with uncommon sugars
Abbreviated Journal Title
J. Med. Chem.
TOPOISOMERASE-I; INDOLOCARBAZOLE GLYCOSIDES; PRACTICAL SYNTHESIS; ANTICANCER AGENT; ANTITUMOR; J-107088; NB-506; FERMENTATION; INHIBITION; SUBSTANCE; Chemistry, Medicinal
Rebeccamycin analogues containing uncommon sugars and substitutions on the imide nitrogen have been synthesized. Their cytotoxicities were tested in colon cancer and leukemia cells. Their ability to target topoisomerase I was examined using the in vivo complex of the topoisomerase bioassay in Hela cells. Compared with aglycon 1, the modified compounds with various sugar moieties showed more potent cytotoxicities and topo I targeting ability. In addition, the rebeccamycin analogues with various uncommon sugars showed distinct cytotoxicities and topo I targeting activities. The activity of compounds with 2-deoxyglucose (8 and 9) > compounds with 2,6-deoxyglucose (5 and 6) > compounds with 2,3,6-deoxyglucose (10). Furthermore, the anticancer activity of compounds correlated with their ability to target endogenous topo I. These results suggest that the sugar moiety, especially the 2-OH and 6-OH group of the sugar, rather than the modifications in imide structure on the indolocarbazole ring, is a key element for its activity.
Journal of Medicinal Chemistry
"Syntheses and biological activities of rebeccamycin analogues with uncommon sugars" (2005). Faculty Bibliography 2000s. 5831.