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New cryptotanshinone derivatives with anti-influenza A virus activities obtained via biotransformation by Mucor rouxii

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Abstract

This paper provides an efficient platform to diversify the structure and pharmaceutical potentials of known natural products. Seven metabolites were obtained via the biotransformation of cryptotanshinone by the fungus Mucor rouxii AS 3.3447, and assigned as 13R-14R-hydroxy-anhydride of 16R-cryptotanshinone (1), 1S-hydroxy-anhydride of 16R-cryptotanshinone (2), 1R-hydroxy-anhydride of 16R-cryptotanshinone (3), 3S-hydroxy-epicryptoacetalide (4), 3S-hydroxy-cryptoacetalide (5), epicryptoacetalide (6), and cryptoacetalide (7). Among these compounds, 1–5 are novel. The ortho-naphthoquinone chromophore of cryptotanshinone was degraded and rearranged by M. rouxii. 1 and 3 showed good anti-influenza A virus activities with the reduced cytotoxic activities compared to the parent substrate cryptotanshinone (8). The structures of all the new compounds were determined on the basis of HRESIMS (high-resolution electrospray ionization mass spectroscopy) spectrometry, NMR (nuclear magnetic resonance) spectroscopy, ECD (electronic circular dichroism) calculations, and the CD (circular dichroism) of “in situ” method with [Rh2(OCOCF3)4].

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (31430002, 81573341, 31400090, 31320103911), the National Major Scientific and Technological Special Project for Significant New Drugs Development of China (2015ZX09J15102-004), the National Institutes of Health (GM40541), the Welch Foundation (F-1511), the European Union’s Seventh Framework Programme (FP7/2007–2013) under grant agreement no. 312184, and the CAMS Innovative Medicine (CAMS-I2M) (No. 2016-I2M-2-002, 2016-I2M-2-003).

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  1. Wenni He and Yao Li contributed equally to this work.

Authors and Affiliations

  1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China

    Wenni He, Yao Li, Yuejie Qin, Xiaomei Tong, Zhijun Song, Yu Zhao, Ran Wei, Huanqin Dai & Xin Ye

  2. China Pharmaceutical Culture Collection, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China

    Wenni He

  3. University of Chinese Academy of Sciences, Beijing, 100049, China

    Yao Li, Zhijun Song & Yu Zhao

  4. Department of Medicinal Chemistry, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China

    Li Li

  5. State Key Laboratory of Mycology Chemistry, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China

    Wenzhao Wang

  6. Department of Natural Products, China Pharmaceutical University, Nanjing, 210009, China

    Houwei Luo

  7. State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai, 200237, China

    Lixin Zhang & Xueting Liu

  8. Laboratory for Marine Biology and Biotechnology, Qingdao National Laboratory for Marine Science and Technology, Shandong, China

    Lixin Zhang

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  1. Wenni He
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Correspondence to Lixin Zhang or Xueting Liu.

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He, W., Li, Y., Qin, Y. et al. New cryptotanshinone derivatives with anti-influenza A virus activities obtained via biotransformation by Mucor rouxii . Appl Microbiol Biotechnol 101, 6365–6374 (2017). https://doi.org/10.1007/s00253-017-8351-0

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