Three new alkaloids from Haplophyllum tuberculatum as competitive type of in-vitro α-glucosidase inhibitors

In a search for new drug-like molecules, we investigated Haplophyllum tuberculatum as a potential source of alpha-glucosidase inhibitors. Three new natural products (2, 6, and 7), and one previously synthesized compound (4), isolated here as a natural product for the first time, were isolated from an ethyl acetate extract. Additionally, six known compounds (1, 3, 5, and 8-10) were also characterized. The structures of all compounds were elucidated by 1D- and 2D-NMR techniques and HR-ESI-MS. All phytochemicals were evaluated for inhibitory activity against alpha-glucosidase and eight natural products (1 and 4-10) exhibited appreciable activities with IC50 values ranging from 2.28 f 0.64-71.10 f 2.47 mu M, whilst 2 and 3 exhibited weak activities with IC50 values of 146.73 f 2.73 and 260.53 f 3.18 mu M, respectively. Compounds 10 (IC50 = 2.28 f 0.64 mu M), 8 (IC50 = 7.16 f 0.23 mu M) and 7 (IC50 = 8.95 f 0.37 mu M) displayed significant inhibition compared to the positive control acarbose (IC50, 875.75 f 1.24 mu M). The alpha-glucosidase inhibitory activities of all compounds are reported here for the first time. Furthermore, kinetic study of the most potent compounds 8 and 10 exhibited concentration dependent type of inhibition. In addition, molecular docking analysis displayed excellent binding of these molecules in the active site of the alpha-glucosidase enzyme and the in-silico results and in vitro analysis were well correlated.