First discovery of sulfonamides derivatives with acetylcholinesterase inhibitory activity in fungus Pestalotiopsis sp. HNY36-1D

Abstract

Three rare natural sulfonamide products, sargassulfamide A (1), together with two unreported sulfonamides pestasulfamides B (2) and A (3) were obtained from mangrove endophytic fungus Pestalotiopsis sp. HNY36-1D under the guidance of chemical and biological autoradiography. Their structures were determined by 1D and 2D NMR, HR-ESI-MS, as well as single crystal X-ray diffraction. It was noteworthy that sulfonamide derivatives were obtained from metabolites of fungi for the first time. In bioassay, compounds 1 and 3 showed moderate acetylcholinesterase (AChE) inhibitory activities with IC50 values 28.41 and 11.94 μM, respectively. The structure-activity relationships (SARs) analysis suggested that the existence of hydrogen atom on the N atom of sulfonamide derivatives and the closed loop of cyclic dipeptide were beneficial to the activity. The molecular docking studies indicated that 1 and 3 were near the center of the active pocket of AChE, while 2 was at the edge of the protein due to the large steric hindrance.