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 K_m and V_max 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.

Graphical abstract