Two new (1, 2) and nine known (3-11) compounds were isolated from the rutaceous plant Haplophyllum tuberculatum and characterised by extensive NMR spectroscopic techniques and HR-ESI-MS. After structural elucidation, nine compounds were evaluated for their ability to inhibit α-glucosidase, a target for the treatment of type-2 diabetes. Among them, three compounds (7, 5 and 1) exhibited noteable inhbition with IC50 values of 3.42 ± 0.12, 5.79 ± 0.28, and 6.75 ± 1.18 μM, respectively, while the remaining six compounds (2-4, 6, 8, and 9) had moderate activity with IC50 values ranging from 12.14 ± 0.35 to 24.60 ± 0.57 μM, compared to the standard drug acarbose (IC50 = 875.75 ± 1.24 μM). A kinetic study of compounds 5 and 7 showed that they exhibited competitive inhibition with Ki values of 4.82 ± 0.0036 and 3.92 ± 0.0062 µM, respectively. Furthermore, a structure-based prediction of the compounds' binding mode suggested that these inhibitors fitted exceptionally well within the active site of the target enzyme, α-glucosidase, forming multiple hydrogen and hydrophobic interactions with its active site residues.
Keywords: Haplophyllum tuberculatum (Forssk.) A.Juss., α-Glucosidase inhibition, Alkaloids and lignans, NMR spectroscopy, In-silico docking.
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