Synthesis and biological evaluation of novel ursolic acid analogues as potential α-glucosidase inhibitors.

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.

[Preliminary application of injectable calcium phosphate cement/poly (lactic-co-glycolic acid) microspheres for extraction site preservation].

OBJECTIVE: To investigate the feasibility of extraction site preservation using injectable calcium phosphate cement (CPC) combine with poly (lactic-co-glycolic acid) (PLGA) microspheres. METHODS: Immediate extraction defects models were created in canine mandibles, and the defects were filled with CPC/PLGA (experimental group, E) , Bio-Oss (positive control, P), non-treatment (blank control, B) respectively. Dogs were sacrificed after 4, 8, 12 weeks post operation. Statistical analysis were conducted using SPSS 19. RESULTS RESULTS: of radiological observation showed that there were not significantly different between groups in 4 and 8 week (P > 0.05). After 12 week,E (114.9 ± 8.4) were not significantly different compared with P (117.4 ± 12.1) (P > 0.05) , both were significantly higher than B (95.0 ± 12.6) (P < 0.05) . Histology examination showed that at 4 week following surgery, the result of newly formed bone was as follow, P[ (87.5 ± 1.5) %] > B[(78.7 ± 2.7)%] > E[(69.2 ± 1.8)%] (P < 0.05). At 8, 12 week, results of P[(94.0 ± 2.3)% and (93.5 ± 1.9) %] and E[ (94.7 ± 1.1) % and (96.0 ± 0.9) %] were better than those of B[ (76.8 ± 3.0)% and (87.0 ± 2.4)%] (P < 0.05). CONCLUSIONS: The effect of CPC/PLGA repair immediate alveolar ridge defects is the same as that of Bio-Oss, and CPC/PLGA can be used as a material in extraction site preservation.