Abstract
Two new nucleotide antibiotics, named sinefungin VA and dehydrosinefungin V, were separated by cation exchange column chromatography and purified by HPLC from the culture broth of Streptomyces sp. K05-0178, together with the known antibiotics, sinefungin, dehydrosinefungin and KSA-9342. The structures of the two novel sinefungin analogs were elucidated by spectroscopic studies, including various NMR and advanced peptide chemical methods. Sinefungin VA consists of adenosine and ornithylvalylalanine, whereas dehydrosinefungin V consists of 4′,5′-dehydroadenosine and ornithylvaline. Sinefungin VA showed potent antitrypanosomal activity with an IC50 value of 0.0026 μg ml−1 in vitro without cytotoxicity against MRC-5 cells. Dehydrosinefungin V showed moderate antitrypanosomal activity (IC50=0.15 μg ml−1).
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Acknowledgements
This study was supported, in part, by funds from the Drugs for Neglected Diseases initiative, Quality Assurance Framework of Higher Education from the Ministry of Education, Culture, Sports, Science and Technology in Japan, and All Kitasato Project Study. We are grateful to Ms Hitomi Sekiguchi and Mr Toshiaki Furusawa for their technical assistance, Dr Hiroshi Honma and Dr Masae Sekine, School of Pharmacy, Kitasato University for amino acid analysis, and Ms Akiko Nakagawa, Dr Kenichiro Nagai and Ms Noriko Sato, School of Pharmacy, Kitasato University for measurements of mass and NMR spectra.
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Niitsuma, M., Hashida, J., Iwatsuki, M. et al. Sinefungin VA and dehydrosinefungin V, new antitrypanosomal antibiotics produced by Streptomyces sp. K05-0178. J Antibiot 63, 673–679 (2010). https://doi.org/10.1038/ja.2010.102
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DOI: https://doi.org/10.1038/ja.2010.102
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