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

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, 1 H NMR, and 13 C NMR spectros...

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Published in:Medicinal chemistry research 2020, Vol.29 (1), p.94-102
Main Authors: Smirnova, Irina E., Petrova, Anastasiya V., Kazakova, Oxana B., Minnibaeva, El’za M., Fedorova, Alexandra A., Tran Van, Loc, Tran Van, Chien, Pham Thi, Ninh, Tran Thi Phuong, Thao, Nguyen Thi, Dung, Thi Thu Nguyen, Ha
Format: Article
Language:English
Subjects:
Acarbose
Amines
Amino acids
Biochemistry
Biomedical and Life Sciences
Biomedicine
Biotechnology
Breast cancer
Cancer
Cell Biology
Colon
Colon cancer
Cytotoxicity
Derivatives
Diabetes mellitus
Esterification
Glucosidase
Heterocyclic amines
Lead compounds
Leukemia
Melanoma
NMR
Non-small cell lung carcinoma
Nuclear magnetic resonance
Original Research
Ovarian cancer
Pharmacology/Toxicology
Small cell lung carcinoma
Triterpenoids
Tumor cell lines
α-Glucosidase
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Summary: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, 1 H NMR, and 13 C 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 IC 50 value of 0.037 μM being about 4800-fold more active than acarbose and 108-fold more active than the native DA with the IC 50 value of 4.0 μM.
ISSN:1054-2523
1554-8120
DOI:10.1007/s00044-019-02462-x