title: Synthesis and antitumor activity of novel C-8 ester derivatives of leinamycin.
abstract: A novel series of C-8 ester derivatives of leinamycin are described. Condensation of N-substituted amino acids or carboxylic acids containing polyether moiety with leinamycin resulted in the C-8 ester derivatives with good antitumor activity in several experimental models. Among these derivatives, compound 4e, which has five ethylene glycol ether units in the C-8 acyl group, showed potent antitumor activity against human tumor xenograft. Combination with the modification of the dithiolanone moiety was applied to these C-8 ester derivatives and some of them also showed good antitumor activity.
authors.affiliation: Pharmaceutical Research Institute, Kyowa Hakko Kogyo Co., Ltd., 1188 Shimotogari, Nagaizumi-cho, Sunto-gun, Shizuoka 411-8731, Japan. ykanda@kyowa.co.jp
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kanda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ashizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kawashima
authors.forename: Shun-ichi
authors.initials: S
authors.lastname: Ikeda
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Tamaoki
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D007769:Lactams; D007941:Leukemia P388 / Q000188:drug therapy; D018942:Macrolides; D051379:Mice; D008819:Mice, Nude; D012510:Sarcoma 180 / Q000188:drug therapy; D013329:Structure-Activity Relationship; D013844:Thiazoles; D013871:Thiones
chemical_list: D000903:Antibiotics, Antineoplastic; D004952:Esters; D007769:Lactams; D018942:Macrolides; D013844:Thiazoles; D013871:Thiones; C059000:leinamycin