title: New geldanamycin analogs from Streptomyces hygroscopicus.
abstract: Geldanamycin (GM) and its analogs are important anticancer agents that inhibit heat shock protein (Hsp) 90, which is a major chaperone protein in cancer cells. Accordingly, based on interest in obtaining novel natural GM derivatives, the potential of Streptomyces hygroscopicus JCM4427, a GM producer, was explored for novel natural GM derivative(s), resulting in the discovery of new GM analogs as a biosynthetic shunt product and intermediates from its fermentation broth. In this study, the fermentation, isolation, structure determination, and biological activity of the compounds, two new tetracyclic thiazinogeldanamycin (1) and 19-hydroxy-4,5-dihydrogeldanamycin (3), together with the three known 4,5-dihydrothiazinogeldanamycin (2), reblastatin (4), and 17-demethoxy-reblastatin (5), are described.
authors.affiliation: Chemical Biology Research Center, KRIBB, 30 Yeongudanji-ro, Ochang-eup, Chungbuk 363-883, Korea.
authors.forename: Cheng-Zhu
authors.initials: CZ
authors.lastname: Wu
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Jang
authors.forename: Jong Seog
authors.initials: JS
authors.lastname: Ahn
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D015394:Molecular Structure; D013302:Streptomyces / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C001277:geldanamycin