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Enhancement of anti-bacterial and anti-tumor activities of pentacyclic triterpenes by introducing exocyclic α,β-unsaturated ketone moiety in ring A

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Abstract

Ursolic acid, oleanolic acid, glycyrrhetinic acid, and betulinic acid, the representatives of pentacyclic triterpenes, were modified by introducing 2-methylene-3-oxo group as exocyclic α,β-unsaturated ketone moiety in ring A. The anti-bacterial and anti-tumor activities of these derivatives were assayed by comparing with the parent compounds. Results indicated that pentacyclic triterpenes carrying 2-methylene-3-oxo group in the ring A exhibited a significant improvement in anti-bacterial activity that was limited to Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis. The four derivatives also showed an increased cytotoxicity against leukemia, lung, and breast cancer cell lines in a dose-dependent manner in vitro. U2 and O2 compounds showed strong apoptotic activities to lung carcinoma cell lines. The results for the first time provided scientific evidence for improvement of anti-bacterial and anti-tumor activities of pentacyclic triterpenes using derivatives of these compounds.

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Acknowledgments

The authors are deeply thankful to the staff members of the analytical center for spectral measurement and activity test centre for cytotoxicity assay of the laboratory of chemistry for natural products of Guizhou Province and Chinese academy of sciences. The authors also thank Dr. Yaacov Ben-David for constructive advice and revision of the manuscript. The work was supported by the National Basic Research 973 Program of China (No. 2012CB722601) and the Major Special Project in Guizhou Province (No. 2013-6006).

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Authors and Affiliations

  1. Ministry of Education Key Laboratory of Green Pesticide and Ago-Bioengineering, Center for Research and Development of Fine Chemicals of Guizhou University, Guiyang, 550025, China

    Li R. Huang & Xiao S. Yang

  2. The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academy of Sciences, Guiyang, 550002, China

    Li R. Huang, Heng Luo, Xiao S. Yang, Lei Chen, Jian X. Zhang, Dao P. Wang & Xiao J. Hao

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  1. Li R. Huang
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  2. Heng Luo
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Correspondence to Xiao S. Yang.

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Li R. Huang and Heng Luo contributed equally to this work.

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Huang, L.R., Luo, H., Yang, X.S. et al. Enhancement of anti-bacterial and anti-tumor activities of pentacyclic triterpenes by introducing exocyclic α,β-unsaturated ketone moiety in ring A. Med Chem Res 23, 4631–4641 (2014). https://doi.org/10.1007/s00044-014-1031-z

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