Abstract
Ursolic acid (UA) is a major pentacyclic triterpenoid in plants, vegetables and fruits, which has been reported to have a potential anti-diabetic activity. Despite various semi-synthetic ursolic acid derivatives already described, new derivatives still need to be designed and synthesized to further improve the anti-diabetic activity. In the present study, two series of novel UA derivatives, were synthesized and their structures were confirmed. The enzyme inhibition activities of semi-synthesized analogues against α-glucosidase were screened in vitro. The results indicated that most of UA derivatives showed a significant inhibitory activity, especially analogues UA-O-i with the IC50 values of 0.71 ± 0.27 μM, which was more potential than other analogues and the positive control. Furthermore, molecular docking studies were also investigated to verify the in vitro study. Structure modification at the C-3 and C-2 positions of UA was an effective approach to obtain the desired ligand from UA, whose structure was in accordance with the active pocket. Besides, suitable hydrophobic group at the position of C-2 might play an important role for the docking selectivity and binding affinity between the ligand and the homology modelling protein. These results could be helpful for designing more potential α-glucosidase inhibitors from UA in the future.
Highlights
Pharmacological activities[23,24,25]
UA analogue compounds UA-01~UA-05 were synthesized according to Fig. 2
Two series of UA derivatives were synthesized at the positions of C-2 and C-3, and their enzyme inhibitory activity assays against α-glucosidase in vitro have been studied
Summary
The potential applications of UA and its analogues for developing novel antidiabetic agent for treatment of DM and its complications are far from being comprehensively exploited. Based on our previous studies, UA and some of its analogues have significant inhibitory activity to α-glucosidase, which might play an important role for treatment of DM and its complications[26,27]. Two series of UA analogues have been described and synthesized. Molecular docking studies were performed with an aim to develop more potential α-glucosidase inhibitory agents. This is the first study associated with the anti-diabetic properties of these new UA analogues, in which α-glucosidase (PDB: 1UOK) was chosen as the docking target
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