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 s ranging from 19 to 129 mu M (ursolic acid IC50 = 29.8 mu M, positive control). Kinetic analysis revealed that albolutein C behaved as a noncompetitive 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 x 10(-4), 1.31 x 10(-4) , and 2.67 x 10(-4) mM, respectively. Molecular dynamic studies indicated that the active compounds remained tied to the enzyme with good binding energy.

Automated summary

Three undescribed compounds, named alboluteins A-C, were isolated from solid rice-based cultures of Malbranchea albolutea. These compounds showed inhibitory activity against PTP1B, with albolutein C behaving as a noncompetitive inhibitor. Docking and molecular dynamic studies indicated that the compounds prefer to bind at the allosteric site of the enzyme, providing insights into their mechanism of action.