Potential α-glucosidase inhibitors from cultures of Biscogniauxia capnodes SWUF15-40 fungus

Abstract

The search for a potent α-glucosidase inhibitor from the fungus Biscogniauxia capnodes SWUF15-40 yielded eighteen compounds. A comprehensive analysis from NMR and MS data revealed three new α-pyrones, biscogniapyrones A–C (1–3), two new isocoumarins (5 and 6), and thirteen known compounds. The configurations were assigned from calculated 13C NMR chemical shifts and ECD spectra, together with 1H NMR analysis of Mosher esters. Several compounds exhibited effective inhibitory activity against α-glucosidase with IC50 values in the range of 0.041–0.257 mM, which are lower than the positive control, acarbose (IC50 0.713 mM). The proposed non-competitive mode of inhibition was deduced from Lineweaver–Burk plots together with Km and Vmax values. In silico dockings of the strongest inhibitor, compound 3 were studied. Three out of the five determined allosteric sites of the enzyme model were favorable, with closed free binding energies of roughly − 4.00 kcal/mol. The binding interactions observed between 3 and amino acids in the pocket sites were hydrogen bonding and hydrophobic interactions. These findings, therefore, provide opportunities for drug development processes to be carried out.