Effects of p-Hydroxybenzaldehyde, Vanillin, and Syringaldehyde on Protein Tyrosine Phosphatase 1B Activity

Background: The protein tyrosine phosphatases phosphatase 1B (PTP 1B) is a negative regulator of insulin signal transduction, and hence, serves as a therapeutic target in the treatment of diabetes. Objective: The present study investigated the inhibitory effects of p-hydroxybenzaldehyde, vanillin, and syringaldehyde on the activity of protein tyrosine phosphatases phosphatase 1B (PTP 1B) in vitro. Methods: The PTP 1B inhibitory assay and mode of inhibition of the three compounds were determined using p-nitrophenyl phosphate (p-NPP) in a 96-well microplate. Molecular docking was used to predict the binding affinities of the compounds with the PTP 1B. Results: The results showed that syringaldehyde exhibited significantly (p< 0.05) higher PTP 1B inhibitory activity (IC50: 12.75 μM) compared to p-hydroxybenzaldehyde (IC50: 33.79 μM) and vanillin (IC50: 42.82 μM) as well as the standards suramin (IC50: 28.35 μM) and ursolic acid (IC50: 19.45 μM). Syringaldehyde and vanillin showed uncompetitive inhibition, whereas p-hydroxybenzaldehyde showed a mixed inhibition type. The molecular docking simulation predicted negative binding energies of -5.0 kcal/mol, -5.5 kcal/mol, and -5.5 kcal/mol for p-hydroxybenzaldehyde, vanillin, and syringaldehyde, respectively. Conclusion: Syringaldehyde showed higher inhibition of PTP 1B compared to other phenolic aldehydes and could be the mechanism of its antidiabetic activity. Hence, further studies are warranted to confirm the efficacy and toxicity of the compound.