Previously unreported monomeric sorbicillinoids from Trichoderma reesei SCNU-F0042 as α-glucosidase inhibitors and antioxidants: isolation, bioactivity, and potential mechanisms.

Diabetes mellitus has caused serious health problems worldwide due to its high prevalence and associated complications. Natural products are considered as an unsurpassed source for lead compounds. This work aims at exploring potential structural leads for the treatment of diabetes mellitus type 2. Five previously unreported monomeric sorbicillinoids (1-3, 5 and 7) and one undescribed 2,4-dihydroxy-5-phenylpentanoic acid (8), together with three known analogues (4, 6 and 9), were isolated and identified based on comprehensive spectroscopic analysis, electronic circular dichroism (ECD) and NMR calculations. All the isolated compounds were screened for antioxidant and α-glucosidase inhibitory activities. The bioassay results disclosed that all the compounds showed significant DPPH and ABTS radical scavenging activity, except for compound 5. Meanwhile, all the compounds exhibited more potent inhibitory effects on α-glucosidase than the marketed drug, acarbose (IC50 234.15 μM), with IC50 values in the range of 16.91-144.47 μM. The enzyme kinetics analysis indicated that compounds 1, 2, and 4 are competitive irreversible inhibitors; compounds 3, 5-7 are competitive reversible inhibitors, while compounds 8 and 9 are non-competitive reversible inhibitors. Spectroscopic investigations indicated the binding of these compounds induced conformational and microenvironmental alterations of α-glucosidase, affecting its catalytic efficiency. In addition, in silico molecular docking was applied to observe the mode of interaction of the active hits within the binding sites of α-glucosidase.