Elucidation of α-glucosidase inhibitory activity and UHPLC-ESI-QTOF-MS based metabolic profiling of endophytic fungi Alternaria sp. BRN05. isolated from seeds of Swietenia macrophylla King

There is a growing demand for new diabetes drugs with fewer side effects to replace current medications known for their adverse effects. Inhibition of α-glucosidase responsible for postprandial hyperglycaemia among diabetes patients is a promising strategy for managing the disease. This study aims to explore and identify novel bioactive molecules with anti-diabetes potential from Alternaria sp. BRN05, an endophytic fungus isolated from a well-known medicinal plant Swietenia macrophylla King. Ethyl acetate extracts of Alternaria sp. BRN05 grown in full-strength (EFS) and quarter-strength (EQS) media respectively were evaluated for their α-glucosidase inhibitory activities. Based on IC ₅₀ values, EQS exhibited significantly greater inhibitory activity (0.01482 ± 1.809 mg/mL) as compared to EFS (1.16 ± 0.173 mg/mL) as well as acarbose control (0.494 ± 0.009 mg/mL). EFS and EQS were subjected to metabolic profiling using Ultra-High-Performance Liquid Chromatography - Electrospray Ionization - Quadrupole Time-of-Flight Mass Spectrometry (UHPLC-ESI-QTOF-MS). A total of nineteen molecules from EFS and twenty from EQS were tentatively identified based on MS/MS fragmentation. Molecular docking analysis revealed that twelve among these exhibited greater binding energies than that of acarbose (-6.6 kcal/mol). Two molecules from EQS, 3’,4’,7-trihydroxyisoflavanone (-7.5 kcal/mol) and alternariol 9-methyl ether (-7 kcal/mol), were subjected to ensemble docking studies, which further strengthened their promise as good α-glucosidase inhibitors for treating diabetes.