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Current Microbiology

, Volume 75, Issue 5, pp 565–573 | Cite as

Identification of a New Uncompetitive Inhibitor of Adenosine Deaminase from Endophyte Aspergillus niger sp.

  • Xin-guo Zhang
  • Jin-wen Liu
  • Peng Tang
  • Zi-yu Liu
  • Guang-Jun Guo
  • Qiao-Yun Sun
  • Jian-jun Yin
Article

Abstract

Adenosine deaminase (ADA) is an enzyme widely distributed from bacteria to humans. ADA is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Endophytes are endosymbionts, often bacteria or fungi, which live within plant tissues and internal organs or intercellular space. Endophytes have a broad variety of bioactive metabolites that are used for the identification of novel natural compounds. Here, 54 morphologically distinct endophyte strains were isolated from six plants such as Peganum harmala Linn., Rheum officinale Baill., Gentiana macrophylla Pall., Radix stephaniae tetrandrae, Myrrha, and Equisetum hyemale Linn. The isolated strains were used for the search of ADA inhibitors that resulted in the identification of the strain with the highest inhibition activity, Aspergillus niger sp. Four compounds were isolated from this strain using three-step chromatography procedure, and compound 2 was determined as the compound with the highest inhibition activity of ADA. Based on the results of 1H and 13C NMR spectroscopies, compound 2 was identified as 3-(4-nitrophenyl)-5-phenyl isoxazole. We showed that compound 2 was a new uncompetitive inhibitor of ADA with high cytotoxic effect on HepG2 and SMCC-7721 cells (the IC50 values were 0.347 and 0.380 mM, respectively). These results suggest that endophyte strains serve as promising sources for the identification of ADA inhibitors, and compound 2 could be an effective drug in the cancer treatment.

Notes

Acknowledgements

This research was supported by the program of the National Natural Science Foundation of China under Grant No. 31360379 and Gansu Province Natural Science Fund (17JR5RA128).

Supplementary material

284_2017_1418_MOESM1_ESM.docx (40 kb)
Supplementary material 1 (DOCX 39 KB)

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Authors and Affiliations

  1. 1.School of Life Science and Engineering, Key Laboratory of Herbal-Tebitan Drug Screening and Deep Processing of Gansu ProvinceLanzhou University of TechnologyLanzhouChina

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