title: Syntheses and biological activities of rebeccamycin analogues with uncommon sugars.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: Guisheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Hao
authors.initials: H
authors.lastname: Cheng
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhu
authors.forename: Lanyan
authors.initials: L
authors.lastname: Fang
authors.forename: Sanzhong
authors.initials: S
authors.lastname: Luo
authors.forename: Mark T
authors.initials: MT
authors.lastname: Muller
authors.forename: Gun Eui
authors.initials: GE
authors.lastname: Lee
authors.forename: Lijun
authors.initials: L
authors.lastname: Wei
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Du
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.forename: Peng George
authors.initials: PG
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002227:Carbazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles; D059004:Topoisomerase I Inhibitors; C053339:rebeccamycin