title: TAN-1323 C and D, new concanamycin-group antibiotics; detection of the angiostatic activity with a wide range of macrolide antibiotics.
abstract: We detected potent angiostatic activity in a MeOH extract from the mycelia of microbial strain S-45628 in the chick chorioallantoic membrane (CAM) assay. The producer was taxonomically characterized as Streptomyces purpurascens. Active principles designated TAN-1323 A-D were isolated and determined to be 18-membered macrolide antibiotics; components C and D are new members of this group, while components A and B are identical to concanamycins C and A, respectively. When tested in the CAM assay, components B and D gave huge avascular zones at the extremely low doses of 10-100 ng/disk, although components A and C showed far weaker activity due to their preferential tissue-damaging effect on the CAM. The discovery that these 18-membered macrolide antibiotics are angiostatic substances prompted us to examine other types of macrolide antibiotics, leading to the discovery that 16-membered macrolide antibiotics such as bafilomycin C1, tylosin and leucomycin also show angiostatic activity on the CAM. Thus, angiostatic potential is widely distributed among macrolide antibiotics. The mechanism of action of these macrolide antibiotics is also discussed.
authors.affiliation: Discovery Research Division, Takeda Chemical Industries, Ltd., Osaka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Hida
authors.forename: S
authors.initials: S
authors.lastname: Iinuma
authors.forename: M
authors.initials: M
authors.lastname: Muroi
authors.forename: Y
authors.initials: Y
authors.lastname: Nozaki
mesh_terms: D016475:3T3 Cells; D000482:Allantois / Q000098:blood supply / Q000187:drug effects; D000818:Animals; D000900:Anti-Bacterial Agents / Q000096:biosynthesis / Q000737:chemistry* / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005285:Fermentation; D006801:Humans; D018942:Macrolides; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D013302:Streptomyces / Q000737:chemistry / Q000145:classification / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D018942:Macrolides; C092165:TAN 1323 C; C092166:TAN 1323 D; C036978:concanamycin A; C036980:concanamycin C