An Integrated Computational Approach for Plant-Based Protein Tyrosine Phosphatase Non-Receptor Type 1 Inhibitors

BACKGROUND: Protein tyrosine phosphatase non-receptor type 1 is a therapeutic target for the type 2 diabetes mellitus. According to the International Diabetes Federation 2015 report, one out of 11 adults suffers from diabetes mellitus globally. OBJECTIVE: Current anti-diabetic drugs can cause life-threatening side-effects. The present study proposes a pipeline for the development of effective and plant-derived anti-diabetic drugs that may be safer and better tolerated. METHODS: Plant-derived protein tyrosine phosphatase non-receptor type 1 inhibitors possessing antidiabetic activity less than 10μM were used as a training set. A common feature pharmacophore model was generated. Pharmacophore-based screening of plant-derived compounds of the ZINC database was conducted using ZINCpharmer. Screened hits were assessed to evaluate their drug-likeness, pharmacokinetics, detailed binding behavior, and aggregator possibility based on their physiochemical properties and chemical similarity with reported aggregators. RESULTS: Through virtual screening and in silico pharmacology protocol isosilybin (ZINC30731533) was identified as a lead compound with optimal properties. This compound can be recommended for laboratory tests and further analyses to confirm its activity as protein tyrosine phosphatase non-receptor type 1 inhibitor. CONCLUSION: The present study has identified plant-derived anti-diabetic virtual lead compound with the potential to inhibit protein tyrosine phosphatase non-receptor type 1, which may be helpful to enhance insulin production. This computer-aided study could facilitate the development of novel pharmacological inhibitors for diabetes treatment.