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Synthesis of dammarenolic acid derivatives with a potent α-glucosidase inhibitory activity

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Abstract

Dammarenolic acid (DA) is an A-seco-dammarane triterpenoids, isolated from Dipterocarpus alatus resin. DA was modified including reactions of esterification and amination with heterocyclic amines and l-amino acids. The structures of new compounds were confirmed by MS, 1H NMR, and 13C NMR spectroscopic analyses and their activities against α-glucosidase and acetylcholinesteras were studied. The cytotoxic activity of DA was screened using a broad panel of 60 human cancer cell lines and it has cytotoxic effect for a variety of human tumor cell lines (leukemia, non-small cell lung cancer, colon cancer, CNS cancer, melanoma, ovarian cancer, renal cancer, breast cancer). All A-seco-dammarane derivatives exhibited very low or no activity against achetylcholinesterase. The majority of new compounds demonstrated higher antidiabetic activity against α-glucosidase compared with starting dammarenolic acid. The methyl dammarenoloate determined as a lead compound with the IC50 value of 0.037 μM being about 4800-fold more active than acarbose and 108-fold more active than the native DA with the IC50 value of 4.0 μM.

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Acknowledgements

The work was carried out under the financial support of the Russian Foundation for Basic Research (project no. 18-53-54005) and the joint-project between Vietnam Academy of Science and Technology (VAST) and Russian Foundation for Basic Research (Project Nr. QTRY01.02/18-19). We thank the National Cancer Institute for the screening of compound 1 on human cancer cell lines.

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Authors and Affiliations

  1. Ufa Institute of Chemistry, UFRC RAS, 71, pr. Oktyabrya, Ufa, 450054, Russia

    Irina E. Smirnova, Anastasiya V. Petrova & Oxana B. Kazakova

  2. Bashkir State University, Zaki Validi 32, Ufa, 450076, Russia

    El’za M. Minnibaeva & Alexandra A. Fedorova

  3. Institute of Chemistry, Vietnamese Academy of Science and Technology, 18 Hoang Quoc Viet Str. Cau Giay Dist., Hanoi, Vietnam

    Loc Tran Van, Chien Tran Van, Ninh Pham Thi, Thao Tran Thi Phuong, Dung Nguyen Thi & Ha Thi Thu Nguyen

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  1. Irina E. Smirnova
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  2. Anastasiya V. Petrova
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  3. Oxana B. Kazakova
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  4. El’za M. Minnibaeva
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  5. Alexandra A. Fedorova
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  6. Loc Tran Van
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  8. Ninh Pham Thi
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  11. Ha Thi Thu Nguyen
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Correspondence to Irina E. Smirnova.

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Smirnova, I.E., Petrova, A.V., Kazakova, O.B. et al. Synthesis of dammarenolic acid derivatives with a potent α-glucosidase inhibitory activity. Med Chem Res 29, 94–102 (2020). https://doi.org/10.1007/s00044-019-02462-x

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  • DOI: https://doi.org/10.1007/s00044-019-02462-x

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