Title:An Integrated Computational Approach for Plant-Based Protein Tyrosine Phosphatase Non-Receptor Type 1 Inhibitors
VOLUME: 13 ISSUE: 4
Author(s):Shabana Bibi and Katsumi Sakata*
Affiliation:Department of Environment and Life Engineering, Graduate School of Engineering, Maebashi Institute of Technology, Maebashi, Department of Environment and Life Engineering, Graduate School of Engineering, Maebashi Institute of Technology, Maebashi, Gunma 371-0816
Keywords:Computer-aided drug design, diabetes mellitus, flavonoids, isosilybin, protein tyrosine phosphatase non-receptor
type 1, common feature pharmacophore modeling, molecular docking, pharmacokinetics.
Abstract: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.
