Molecular docking, chemo-informatic properties, alpha-amylase, and lipase inhibition studies of benzodioxol derivatives

Abstract

AbstractCurrently, available therapies for diabetes could not achieve normal sugar values in a high percentage of treated patients. In this research project, a series of 17 benzodioxole derivatives were evaluated as antidiabetic agents; that belong to three different groups were evaluated against lipase and alpha-amylase (α-amylase) enzymes. The results showed that 14 compounds have potent inhibitory activities against α-amylase with IC50 values below 10 µg/ml. Among these compounds, 4f was the most potent compound with an IC50 value of 1.11 µg/ml compared to the anti-glycemic agent acarbose (IC50 6.47 µg/ml). On the contrary, these compounds showed weak or negligible activities against lipase enzyme. However, compound 6a showed the best inhibitory anti-lipase activity with IC50 44.1 µg/ml. Moreover, all the synthesized compounds were undergone Molinspiration calculation, and the result showed that all compounds obeyed Lipinski’s rule of five. Molecular docking studies were performed to illustrate the binding interactions between the benzodioxole derivatives and α-amylase enzyme pocket. Related to the obtained results it was clear that the carboxylic acid, benzodioxole ring, halogen or methoxy substituted aryl are important for the anti-amylase activities. The potent inhibitory results of some of the synthesized compounds suggest that these molecules should go further in vivo evaluation. It also suggests the benzodioxole derivatives as lead compounds for developing new drug candidates.