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Medicinal Chemistry Research

, Volume 29, Issue 1, pp 94–102 | Cite as

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

  • Irina E. SmirnovaEmail author
  • Anastasiya V. Petrova
  • Oxana B. Kazakova
  • El’za M. Minnibaeva
  • Alexandra A. Fedorova
  • Loc Tran Van
  • Chien Tran Van
  • Ninh Pham Thi
  • Thao Tran Thi Phuong
  • Dung Nguyen Thi
  • Ha Thi Thu Nguyen
Original Research
  • 58 Downloads

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.

Keywords

Triterpenoids Dammaranes Dammarenolic acid Antidiabetic activity Cytotoxicity Achetylcholinesterase activity 

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2462_MOESM1_ESM.pdf (1.4 mb)
Supplementary Material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Irina E. Smirnova
    • 1
    Email author
  • Anastasiya V. Petrova
    • 1
  • Oxana B. Kazakova
    • 1
  • El’za M. Minnibaeva
    • 2
  • Alexandra A. Fedorova
    • 2
  • Loc Tran Van
    • 3
  • Chien Tran Van
    • 3
  • Ninh Pham Thi
    • 3
  • Thao Tran Thi Phuong
    • 3
  • Dung Nguyen Thi
    • 3
  • Ha Thi Thu Nguyen
    • 3
  1. 1.Ufa Institute of Chemistry, UFRC RASUfaRussia
  2. 2.Bashkir State UniversityUfaRussia
  3. 3.Institute of ChemistryVietnamese Academy of Science and TechnologyHanoiVietnam

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