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Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus Nigrospora sp. QQYB1

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Abstract

Marine microorganisms have long been recognized as potential sources for drug discovery. Griseofulvin was one of the first antifungal natural products and has been used as an antifungal agent for decades. In this study, 12 new griseofulvin derivatives [(±)-1−2, (+)-3, (±)-4, 10−12, and 14−15] and two new griseofulvin natural products (9 and 16) together with six known analogues [(−)-3, 5−8, and 13] were isolated from the mangrove-derived fungus Nigrospora sp. QQYB1 treated with 0.3% NaCl or 2% NaBr in rice solid medium. Their 2D structures and absolute configurations were established by extensive spectroscopic analysis (1D and 2D NMR, HRESIMS), ECD spectra, computational calculation, DP4 + analysis, and X-ray single-crystal diffraction. Compounds 1−4 represent the first griseofulvin enantiomers with four absolute configurations (2S, 6'S; 2R, 6'R; 2S, 6'R; 2R, 6'S), and compounds 9−12 represent the first successful production of brominated griseofulvin derivatives from fungi via the addition of NaBr to the culture medium. In the antifungal assays, compounds 6 and 9 demonstrated significant inhibitory activities against the fungi Colletotrichum truncatum, Microsporum gypseum, and Trichophyton mentagrophyte with inhibition zones varying between 28 and 41 mm (10 μg/disc). The structure−activity relationship (SAR) was analyzed, which showed that substituents at C-6, C-7, C-6' and the positions of the carbonyl and double bond of griseofulvin derivatives significantly affected the antifungal activity.

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Data availability

The data that support the findings of this study are included in this published article (and its supplementary information files).

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Acknowledgements

This research was funded by the Guangdong Marine Economy Development Special Project (GDNRC[2022]35, GDNRC[2023]39) and the National Natural Science Foundation of China (U20A2001, 42276114).

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Authors and Affiliations

  1. School of Chemistry, Sun Yat-sen University, Guangzhou, 510275, China

    Ge Zou, Wencong Yang, Tao Chen, Zhaoming Liu, Yan Chen, Taobo Li, Bing Sun, Bo Wang & Zhigang She

  2. State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Institute of Microbiology, Guangdong Academy of Sciences, Guangzhou, 510070, China

    Zhaoming Liu

  3. School of Pharmacy, Anhui Medical University, Hefei, 230032, China

    Yan Chen

  4. Department of Chemistry, Women University Swabi, Swabi, 23430, Pakistan

    Gulab Said

Authors
  1. Ge Zou
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  3. Tao Chen
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  5. Yan Chen
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  8. Bing Sun
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  10. Zhigang She
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Contributions

ZG performed the experiments and wrote the paper; LZ provided the pathogenic fungi; YW, CT, and LT participated in the experiments; LZ and CY analyzed the data and discussed the result; SG revised the manuscript; SB and WB reviewed the manuscript and SZ designed and supervised the experiments. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Bing Sun, Bo Wang or Zhigang She.

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Conflict of interest

The authors declare that they have no conflict of interest. Zhigang She is one of the Editorial Board Members, but he was not involved in the journal’s review of, or decision related to, this manuscript.

Animal and human rights statement

This article does not contain any studies with human participants or animals performed by the authors.

Additional information

Edited by Chengchao Chen.

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Supplementary file 1 (DOCX 604 KB)

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Zou, G., Yang, W., Chen, T. et al. Griseofulvin enantiomers and bromine-containing griseofulvin derivatives with antifungal activity produced by the mangrove endophytic fungus Nigrospora sp. QQYB1. Mar Life Sci Technol 6, 102–114 (2024). https://doi.org/10.1007/s42995-023-00210-0

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