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Complete NMR assignment and absolute configuration of k4610422, a norditerpenoid inhibitor of testosterone-5α-reductase originally from Streptosporangium: rediscovery from a thermophilic Actinomadura

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Abstract

A norditerpenoid k4610422 (1), an inhibitor of testosterone-5α-reductase originally discovered from a mesophilic rare actinomycete of the genus Streptosporangium, was isolated from the culture extract of a thermophilic actinomycete Actinomadura sp. The complete 1H and 13C NMR assignment and absolute configuration of 1 were addressed by spectroscopic measurements including NOESY and CD spectra coupled with ECD calculation, which allowed to establish the (5 R,9 S,10 R,13 S)-configuration. Compound 1 was moderately cytotoxic against P388 murine leukemia cells with IC50 30 μM.

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Acknowledgements

We thank Drs K. Monde and T. Taniguchi at Hokkaido University for theoretical ECD calculation and Drs Y Hikichi and A. Kanda at Kochi University for providing R. solanacearum SUPP1541. P388 cells were obtained from JCRB Cell Bank under an accession code JCRB0017 (Lot. 06252002). This research was supported by JSPS KAKENHI grant no. JP16K07719 to Y.I.

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Authors and Affiliations

  1. Biotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan

    Hirofumi Akiyama, Naoya Oku, Enjuro Harunari & Yasuhiro Igarashi

  2. Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Watanalai Panbangred

  3. Mahidol University – Osaka University Collaborative Research Center on Bioscience and Biotechnology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Watanalai Panbangred

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  1. Hirofumi Akiyama
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  2. Naoya Oku
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  3. Enjuro Harunari
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  4. Watanalai Panbangred
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  5. Yasuhiro Igarashi
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Correspondence to Yasuhiro Igarashi.

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Akiyama, H., Oku, N., Harunari, E. et al. Complete NMR assignment and absolute configuration of k4610422, a norditerpenoid inhibitor of testosterone-5α-reductase originally from Streptosporangium: rediscovery from a thermophilic Actinomadura. J Antibiot 73, 60–65 (2020). https://doi.org/10.1038/s41429-019-0231-7

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