Pentacylic triterpenes from Lavandula coronopifolia: structure related inhibitory activity on α-glucosidase

Abstract

Ten pentacyclic triterpenes (1-10) were isolated from Lavandula coronopifolia. We evaluated their a-glucosidase inhibitory activity, and found that the aglycones, 1, 2, 3, 4, 7 and 10 showed superior IC50 values to the positive control. In order to explain the structural requirements for a-glucosidase inhibitory activity, eleven derivatives were prepared, including one new compound, 2-formyl-( A)1–19a-hydroxy-1-norursane-2, 12-dien-28-oic acid 10c. The results demonstrated that a free hydroxyl at ring-A and a free carboxylic group at position 28 are key structural features for the a-glucosidase inhibitory activity, also that an ursane skeleton is optimum for the activity. Additionally, enzyme kinetic analysis of pomolic acid 2, the most potent compound, revealed that it inhibited a-glucosidase in a mixed-type manner. The molecular docking simulation validated this type of inhibition and highlighted the role of the C-3 hydroxyl and C-28 carboxylic groups in interaction with the enzyme in silico.