著者

吉田 健一郎 東 龍太郎 佐伯 真由子 南 慶典 大谷 敏夫

出版者

天然有機化合物討論会実行委員会

雑誌

天然有機化合物討論会講演要旨集 35 (ISSN:24331856)

巻号頁・発行日

pp.250-257, 1993-09-10 (Released:2017-08-18)

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Antibiotic C-1027, a novel antitumor chromoprotein isolated from the broth filtrate of Streptomyces globisporus C-1027, shows extremely potent cytotoxicity against KB carcinoma cells (IC_<50> 0.1ng/ml) in vitro and antitumor activity toward tumor-bearing mice in vivo. These activities are correlated with the ability of the antibiotic to cause DNA double-strand scission. The antibiotic consists of an apoprotein and a labile chromophore (C-1027-Chr) that is responsible for the biological activity of C-1027. The chromophore is readily separated from its apo-protein by extraction, but the exceeding instability in the protein-free state hampered the structure elucidation. The similar situation has been also observed in the other chromoprotein antibiotics of this family such as neocarzinostatin (NCS), macromomycin, auromomycin (AUR), actinoxanthin and kedarcidin. Among them, NCS is the only one whose chromophore structure has been elucidated, and very recently, the structural novelty of kedarcidin chromophore has been disclosed by the Bristol-Myers Squibb group. We have characterized an inactive but more stable reaction product (2) of C-1027-Chr, which was prepared by treatment of C-1027-Chr in ethanol. It possesses a macrocyclic structure together with oxazolinate and aminosugar moieties as side chains. Its benzodihydropentalene core structure suggested to us the presence of an enediyne in the native C-1027-Chr. We disclose herein the novel structure of C-1027-Chr (1) and the cycloaromatization mechanism leading to product (2), which would explain its extreme potency in terms of cytotoxicity and ability to cause DNA double-strand scission.