Journal
CURRENT COMPUTER-AIDED DRUG DESIGN
Volume 13, Issue 4, Pages 319-335Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1573409913666170406145607
Keywords
Computer-aided drug design; diabetes mellitus; flavonoids; isosilybin; protein tyrosine phosphatase non-receptor type 1; common feature pharmacophore modeling; molecular docking; pharmacokinetics
Funding
- Otsuka Toshimi Scholarship Foundation, Japan
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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 10 mu M 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.
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