α-Glucosidase inhibitors from a mangrove associated fungus, Zasmidium sp. strain EM5-10

BACKGROUND: Mangroves plants and their endophytes represent a natural source of novel and bioactive compounds. In our ongoing research on mangrove endophytes from the Panamanian Pacific Coast, we have identified several bioactive endophytic fungi. From these organisms, an isolate belonging to the genus Zasmidium (Mycosphaerellaceae) showed 91.3% of inhibition against α-glucosidase enzyme in vitro. RESULTS: Zasmidium sp. strain EM5-10 was isolated from mature leaves of Laguncularia racemosa, and its crude extract showed good inhibition against α-glucosidase enzyme (91.3% of inhibition). Bioassay-guided fractionation of the crude extract led to obtaining two active fractions: L (tripalmitin) and M (Fungal Tryglicerides Mixture). Tripalmitin (3.75 µM) showed better inhibitory activity than acarbose (positive control, IC(50) 217.71 µM). Kinetic analysis established that tripalmitin acted as a mixed inhibitor. Molecular docking and molecular dynamics simulations predicted that tripalmitin binds at the same site as acarbose and also to an allosteric site in the human intestinal α-glucosidase (PDB: 3TOP). CONCLUSIONS: Zasmidium sp. strain EM5-10 represents a new source of bioactive substances that could possess beneficial properties for human health.