Inflammation and diabetic inhibitors from Amanita abrupta and Amanita pantherina: experimental and computational results

This study investigates potential inhibitors of nitric oxide (NO) production, α-glucosidase, and protein tyrosine phosphatase 1B (PTP1B) from Amanita abrupta and Amanita pantherina. Sixteen compounds (1–16) were isolated by chromatographic techniques and high-performance liquid chromatography (HPLC), and their structures were elucidated by nuclear magnetic resonance (NMR) and literature comparison. Biological activities were evaluated via in vitro assays: the Griess assay for NO inhibition, the p-nitrophenol assay for α-glucosidase, and enzymatic assays for PTP1B. Molecular docking was employed to investigate protein–ligand interactions. The isolates included alanine (1), threonine (2), 2-amino-4-pentynoic acid (3), 4-hydroxy-2-pyrrolidinone (4), ibotenic acid (5), serotonin (6), uracil (7), hypoxanthine (8), bufotenine (9), β-sitosterol (10), stigmasterol (11), cycloeucalenol (12), spinasterol (13), daucosterol (14), stigmasterol-3-O-β-D-glucoside (15), and betulin (16). Compounds 1 and 2 exhibited weak NO inhibition (IC₅₀ = 68.76 and 52.47 μM). Compound 14 displayed the strongest α-glucosidase inhibition (IC₅₀ = 10.56 μM), while compounds 10–13 and 16 showed moderate effects (IC₅₀ = 19.52–32.14 μM). Serotonin (6) also had moderate activity (IC₅₀ = 78.23 μM). For PTP1B inhibition, betulin (16) was most potent (IC₅₀ = 16.80 μM), followed by compounds 10, 11, and 13 with weaker activities (IC₅₀ = 36.28–48.17 μM). Overall, selected compounds (1, 2, 10–14, and 16) exhibited promising bioactivities, warranting further docking studies against inducible nitric oxide synthase (iNOS), PTP1B, and 3AJ7. ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions supported favorable pharmacokinetic properties and potential drug-likeness, highlighting these molecules as leads for anti-inflammatory and anti-diabetic drug discovery.