title: Antitumor activity of novel ailanthone derivatives in vitro and in vivo.
abstract: The antitumor activities of two ailanthone derivatives with 15 beta-acyloxy side chains were investigated. The cytotoxic activity of 11 beta, 20-epoxy-1 beta, 11 alpha, 12 alpha-trihydroxy-15-beta-[E)-3-methyl-2-octenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN2071) and 11 beta, 20-epoxy-1 beta, 11 alpha, 12 alpha-trihydroxy-15 beta-[E)-2-undecenoyl) oxypicras-3,13(21)-diene-2,16-dione (SUN0237) was close to that of bruceantin and vincristine. SUN2071 was shown to be a potent inhibitor of protein synthesis in L1210 cultured cells. When administered i.p. to i.p. inoculated P388 leukemia mice, daily treatment with SUN2071 and SUN0237 significantly increased the lifespan (increases in lifespan in excess of 100% were achieved). These increases were comparable to those achieved with vincristine. The therapeutic ratio of SUN2071 was also close to that of vincristine. However, the compounds were ineffective when administered as a single injection. Daily i.p. treatment with SUN2071 demonstrated significant tumor growth inhibition in mice inoculated s.c. with colon-38 and moderate activity against i.p. L1210 leukemia and i.p. B16 melanoma. The compounds were ineffective when tested against the Lewis lung carcinoma and colon-26. In a preliminary toxicological study, SUN2071 at a therapeutic dose in daily consecutive i.p. injection produced leucopenia.
authors.affiliation: Laboratory of Chemotherapy and Internal Medicine, Aichi Cancer Center, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: Y
authors.initials: Y
authors.lastname: Suzumura
authors.forename: M
authors.initials: M
authors.lastname: Fukushima
authors.forename: T
authors.initials: T
authors.lastname: Honda
authors.forename: T
authors.initials: T
authors.lastname: Nakanishi
authors.forename: T
authors.initials: T
authors.lastname: Noguchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D005260:Female; D005900:Glaucarubin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D007939:Leukemia L1210 / Q000188:drug therapy*; D007941:Leukemia P388 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008546:Melanoma, Experimental / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010616:Phenanthrenes / Q000627:therapeutic use*; D036702:Quassins; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D010616:Phenanthrenes; D036702:Quassins; D012334:RNA, Neoplasm; D014750:Vincristine; C057386:SUN 0237; C057385:SUN 2071; D005900:Glaucarubin; C002550:bruceantin