Bioactive Compounds from Brachychiton diversifolius Peel as Potential Inhibitors of Protein Tyrosine Phosphatase: Implications for Diabetes Therapy

Abstract

The Brachychiton diversifolius is among the widely employed plants in conventional systems of medicine in numerous therapies, especially in the management of metabolic disorders such as diabetes. The tyrosine phosphorylation is important in glucose homeostasis and insulin signaling and the protein tyrosine phosphatase is an important target in the development of antidiabetic treatment. This investigation aimed at determining bioactive elements of the methanolic leaf extract of B. diversifolius and testing their inhibitory capacity against protein tyrosine phosphatase. Using the gas chromatography-mass spectrometry (GC-MS), eight individual phytocompounds were detected in the methanolic leaf extract of B. diversifolius. The drug-likeness and pharmacokinetics of each compound were analyzed using SwissADME web program. The findings were complete agreement with the Rule of Five of Lipinski, having good oral bioavailability and drug-like characteristics. Moreover, binding affinity against protein tyrosine phosphatase was determined by performing molecular docking with the PyRx virtual screening tool. Interaction analysis was done through the Discovery Studio Visualizer. The docking outcome showed that there are a few phytocompounds with robust binding affinities with the active site of protein tyrosine phosphatase. Acridin-9-yl (4-nitro-phenyl) was the compound with the highest binding affinity that showed good binding scores with the target protein followed by 3-Hydroxy-4-Methoxy-6-Methylflavone, 3 (3-Bromophenyl) propenone, and 1-Benzylindole. The results aid in proving the presence of bioactive compounds in the leaves of Brachychiton diversifolius that have significant inhibitory effects against protein tyrosine phosphatase, which validates the use of the leaves in the treatment of diabetes. Nevertheless, future in vitro and in vivo studies are recommended to establish the therapeutic efficacy of the identified compounds.