Abstract
In the course of screening for antimalarial agents, five tropolone compounds were isolated from the culture broth of Penicillium sp. FKI-4410. Two were known compounds, puberulic acid and stipitatic acid. Three were new analogs of puberulic acid, designated viticolins A–C. Among them, puberulic acid exhibited potent antimalarial inhibition, with IC50 values of 0.01 μg ml−1 against chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro. Furthermore, puberulic acid showed weak cytotoxicity against human MRC-5 cells, with an IC50 value of 57.2 μg ml−1. The compound also demonstrated a therapeutic effect in vivo, which compared well against the currently used antimalarial drugs, and thus shows promise as a leading candidate for development into a new antimalarial compound.
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Acknowledgements
This study was supported, in part, by funds from the Quality Assurance Framework of Higher Education from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) in Japan, and the All Kitasato Project Study. We are grateful to Ms Hitomi Sekiguchi and Mr Toshiaki Furusawa for their technical assistance and to Ms Akiko Nakagawa, Dr Kenichiro Nagai and Ms Noriko Sato, School of Pharmacy, Kitasato University for measurements of mass and NMR spectra. We also thank Dr Shinichi Kondo (Bioscience Associates) for providing 7-hydroxytropolone.
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Iwatsuki, M., Takada, S., Mori, M. et al. In vitro and in vivo antimalarial activity of puberulic acid and its new analogs, viticolins A–C, produced by Penicillium sp. FKI-4410. J Antibiot 64, 183–188 (2011). https://doi.org/10.1038/ja.2010.124
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DOI: https://doi.org/10.1038/ja.2010.124
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