Molecular docking and inhibition studies of α-amylase activity by labdane diterpenes from Alpinia nigra seeds

Wide varieties of synthetic drugs are available for combating type 2 diabetes but are not free of associated side effects. Commercially available antidiabetic drugs are known to be potent inhibitors of alpha-amylase which reduce postprandial hyperglycaemia. Here, we have investigated Alpinia nigra seed extracts and the isolated two labdane diterpenes (I and II) for the a-amylase inhibitory activity. These labdane type diterpenes showed more promising inhibitory effects (IC50 value 24.3 +/- 2.05 and 15.167 +/- 0.52 mu M for compound I and II, respectively) against alpha-amylase than the standard inhibitor, acarbose. For both compounds, the mode of enzymatic inhibition was found to be non-competitive with K-i 13.303 +/- 0.065 and 12.19 +/- 0.099 mu M, respectively. Molecular docking studies revealed that both I and II bind the human pancreatic a-amylase in the active site cleft similar to the acarbose. Among all the compounds under investigation, acarbose and compound II were found to have the highest MolDock and re-rank score. Further molecular dynamic simulation studies also supports the docking results obtained for both I and II. This is the first report on a-amylase inhibitory effect of the two labdane diterpenes with their potential candidature as future antidiabetic drugs of herbal origin.