title: Antitumour activity of new semi-synthetic anthracyclines containing fluorotalopyranose.
abstract: The authors have synthesized 7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone (FT-ADM) which exhibited strong antitumour activity and weak toxicity. These characteristics of FT-ADM are partly due to the presence of a 2'-fluoro atom which strengthens the glycoside bond. FT-ADM, however, is sparingly soluble in water because of lack of the 3'-amino group of adriamycin. To increase the solubility of FT-ADM, a hydrophilic group was added at the 14-OH group. Then, the 14-hemisuccinate, 14-hemiglutarate, 14-hemiadipiate, 14-hemipimelate and 14-hemisuberate derivatives of FT-ADM were synthesized. Among them, the 14-hemipimelate derivative (FAD-104) was selected for further development because of its potent antitumour activity and weak toxicity. When drugs were injected intraperitoneally every day from day 1 to 9, FAD-104 showed an apparently stronger antitumour effect against mouse L-1210 leukaemia than adriamycin with lower toxicities. FAD-104 was also more effective than adriamycin on L-1210 using other administration schedules. A characteristic feature is that FAD-104 is effective over a very broad range, which will be advantageous for safe clinical use. FAD-104 also showed marked antitumour effect against L-1210 when it was injected intravenously either once on day 1 or three times on days 1, 5 and 9. Thus, FAD-104 may be a more potent antitumour anthracycline than adriamycin.
authors.affiliation: Institute of Microbial Chemistry, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
authors.forename: T
authors.initials: T
authors.lastname: Takeuchi
authors.forename: K
authors.initials: K
authors.lastname: Komuro
authors.forename: C
authors.initials: C
authors.lastname: Nosaka
authors.forename: S
authors.initials: S
authors.lastname: Kunimoto
authors.forename: T
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Y
authors.initials: Y
authors.lastname: Takagi
authors.forename: S
authors.initials: S
authors.lastname: Umezawa
authors.forename: H
authors.initials: H
authors.lastname: Umezawa
mesh_terms: D000818:Animals; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy*; D051379:Mice
chemical_list: C049732:7-O-(2,6-dideoxy-2-fluorotalopyranose)adriamycinone; C049731:7-O-(2,6-dideoxy-2-fluorotalopyranosyl)daunomycinone; D004317:Doxorubicin; D003630:Daunorubicin