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 nonreceptor
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.