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Overview
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Background
UK 1, an unusual bis-benzoxazole metabolite isolated from Streptomyces sp. 517-02, is an inhibitor of topoisomerase II (Topo II) and hepatitis C viral replication. It is an antifungal and an antibiotic, and displays a wide spectrum of potent anticancer activities against lymphoma, leukemia, and certain solid tumor-derived cell lines with IC50 values as low as 20 nM. However, UK 1 is devoid of antimicrobial activity and is inactive against Pseudomonas aeruginosa and Staphylococcus aureus, a methicillin-resistant strain of S. aureus. Additionally, UK-1 can bind a wide variety of di- and tri-valent metal ions, particularly Mg2+ ions, and form complexes with DNA in the presence of Mg2+ ions. Topo II are ATP-dependent enzymes, which can simultaneously cut both strands of the DNA helix to manage DNA supercoils and tangles.
In vitro: UK 1 strongly blocked the growth of human epitheloid carcinoma HeLa, mouse melanoma B16, mouse leukemia P388 cells with ED50 values of 1.22 μg/ml, 1.17 μg/ml, and 0.11 μg/ml, respectively. UK 1 did not display any growth inhibitory activity against bacteria, fungi and yeasts up to 100 μg/ml [1].
In vivo: Up to now, in vivo study of UK 1 is still in the development stage.
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