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 alpha-pyranones, one known mellein derivative, one known sesquiterpenoid, as well as two known methyl 2hydroxypropanoate derivatives were isolated from the KM solid medium culture of an endophytic fungus Pestalotiposis palmarum, which has previously produced diphenyl ether derivatives and alpha-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 alpha-glucosidase, acetylcholinesterase inhibitory activities, and cytotoxic activities. Notably, in vitro bioassays revealed that compound 1 exhibited threefold higher alpha-glucosidase inhibitory activity than acarbose, with IC50 values of 512.4 mu M. Furthermore, the possible alpha-glucosidase inhibitory mechanisms involved were also studied by molecular docking.