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

Dammarenolic acid (DA) is an A-seco- dammarane triterpenoids, isolated from Dipterocarpus alatusresin. DA was modified including reactions of esterification and amination with heterocyclic aminesand l-amino acids. The structures of new compounds were confirmed by MS, 1H NMR, and 13C NMR spectroscopic analyses and their activities against α- glucosidaseand 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- dammaranederivatives exhibited very low or no activity against achetylcholinesterase. The majority of new compounds demonstrated higher antidiabetic activity against α- glucosidasecompared with starting dammarenolic acid. The methyl dammarenoloate determined as a lead compoundwith the IC50 value of 0.037 μM being about 4800-fold more active than acarboseand 108-fold more active than the native DA with the IC50 value of 4.0 μM.