A new phthalides derivative pestalotiophthalide a with α-glucosidase inhibitory activity from Pestalotiopsis palmarum

Three phthalide derivatives, including an undescribed congener, pestalotiophthalide A (1), together with seven known α-pyranones, one known mellein derivative, one known sesquiterpenoid, as well as two known methyl 2-hydroxypropanoate derivatives were isolated from the KM solid medium culture of an endophytic fungus Pestalotiposis palmarum, which has previously produced diphenyl ether derivatives and α-pyrones when cultured under solid rice medium. Their structures were elucidated on the basis of 1D and 2D NMR, HRESIMS spectroscopic data. Pestalotiophthalide A was acquired as a pair of inseparable diasteriomeric epimers due to the chiral carbon of hemiketal at C-3. This common phenomenon stem from the ring-chain tautomerism of the hemiketal functional moiety in solution, which was testified through chiral HPLC analysis. All compounds were evaluated for α-glucosidase, acetylcholinesterase inhibitory activities, and cytotoxic activities. Notably, in vitro bioassays revealed that compound 1 exhibited threefold higher α-glucosidase inhibitory activity than acarbose, with IC50 values of 512.4 μM. Furthermore, the possible α-glucosidase inhibitory mechanisms involved were also studied by molecular docking.