Synthesis of dammarenolic acid derivatives with a potent α-glucosidase inhibitory activity
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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.
KeywordsTriterpenoids Dammaranes Dammarenolic acid Antidiabetic activity Cytotoxicity Achetylcholinesterase activity
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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Conflict of interest
The authors declare that they have no conflict of interest.
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