Protein tyrosine phosphatase 1B inhibitors from the fungus Malbranchea albolutea

From solid rice-based cultures of Malbranchea albolutea, three undescribed ardeemins and sartoryglabrins analogs were discovered and named alboluteins A-C. 1H-Indole-3-carbaldehyde, and anthranilic acid were also isolated. 1D and 2D-NMR techniques, as well as DFT-calculated chemical shifts, allowed characterizing alboluteins A-C. Testing these compounds against PTP1B indicated their inhibitory activity with IC₅₀'s ranging from 19 to 129 μM (ursolic acid IC₅₀ = 29.8 μM, positive control). Kinetic analysis revealed that albolutein C behaved as a non-competitive inhibitor. Docking studies of alboluteins A-C into the crystal structure of PTP1B (PDB ID: 1T49) predicted that all compounds prefer to bind at the allosteric site of the enzyme, with Ki values of 2.02 × 10^-4, 1.31 × 10^-4, and 2.67 × 10^-4 mM, respectively. Molecular dynamic studies indicated that the active compounds remained tied to the enzyme with good binding energy.