Protein tyrosine phosphatase 1B inhibitors from the fungus Malbranchea albolutea

• Published in: Phytochemistry (Oxford) Vol. 184; p. 112664
• Main Authors: Díaz-Rojas, Miriam, Raja, Huzefa, González-Andrade, Martin, Rivera-Chávez, José, Rangel-Grimaldo, Manuel, Rivero-Cruz, Isabel, Mata, Rachel
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.04.2021; Elsevier
• Subjects: Alboluteins A-C; Ardeemins; Biochemistry & Molecular Biology; Diabetes; Enzyme Inhibitors - pharmacology; Fungi - metabolism; Kinetics; Life Sciences & Biomedicine; Malbranchea albolutea; Molecular Docking Simulation; Onigenaceae; Onygenales; Plant Sciences; Protein tyrosine phosphatase 1B; Protein Tyrosine Phosphatase, Non-Receptor Type 1 - metabolism; Science & Technology; Malbranchea albolutea; Protein tyrosine phosphatase 1B; Alboluteins A-C; Diabetes; Ardeemins; Onigenaceae
• ISSN: 0031-9422; 1873-3700
• DOI: 10.1016/j.phytochem.2021.112664

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. [Display omitted] Alboluteins A-C were isolated from Malbranchea albolutea.Alboluteins A-C inhibited protein tyrosine phosphatase 1B.Alboluteins A-C have potential as antidiabetic agents.