Mechanistic insight into the interactions between thiazolidinedione derivatives and PTP-1B combining 3D QSAR and molecular docking in the treatment of type 2 diabetes
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Adedoyin Igunnu
and
Temidayo Olamide Adigun
Abstract
Protein tyrosine phosphatases (PTP) regulate various cellular processes and represent important targets for therapeutic intervention in various diseases. Studies have shown that partial or total cessation of the PTP-1B gene in normal and diabetic mice has led to resistance to weight gain and improved insulin response. Also, a further study showed that inhibition of PTP-1B or a reduction in its cellular abundance in mice resulted in similar effects and, as such, provided a rationale for the treatment strategy for type 2 diabetes. Thiazolidinedione (TZD) derivatives have been identified as new PTP-1B inhibitors but the mechanism of interaction between TZD derivatives and PTP-1B is still elusive. In this study, a three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was performed, including multiple linear regression (MLR) and cross-validation, on a set of TZD derivatives as antidiabetic agents. MLR analysis was performed on 23 PTP-1B TZD derivatives to determine the relationships between physicochemical properties and antidiabetic properties of TZD derivatives. The training data set creates a QSAR model with a correlation coefficient (R2) of 0.8516, a Q2 (Leave-One-Out) cross-validation factor of 0.6473, r2 (correlation coefficient) for the external dataset is 0.8367 while r2 of predicted dataset is 0.8934 by the MLR Method. The MLR model was also validated by the standardization approach. We observed a high correlation between predicted and observed activity (experimental values), thus confirming and proving the high quality of QSAR models. Finally, molecular docking analysis was performed to better understand the interactions between the PTP-1B target and TZD derivatives. The model proposed in this project can be used to design new TZD derivatives with specific PTP-1B inhibitory activity.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Research funding: None declared.
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Conflict of interest: The authors declare that they have no competing interests.
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© 2020 Walter de Gruyter GmbH, Berlin/Boston
Articles in the same Issue
- Frontmatter
- Reviews
- A computational study of the SNAr reaction of 2-ethoxy-3,5-dinitropyridine and 2-methoxy-3,5-dinitropyridine with piperidine
- Review of research of nanocomposites based on graphene quantum dots
- Atomistic insight into the significantly enhanced photovoltaic cells of monolayer GaTe2 via two-dimensional van der Waals heterostructures engineering
- Mechanistic insight into the interactions between thiazolidinedione derivatives and PTP-1B combining 3D QSAR and molecular docking in the treatment of type 2 diabetes
- Structural and spectroscopic properties of 3-halogenobenzaldehydes: DFT and TDDFT simulations
- Understanding (coupled) large amplitude motions: the interplay of microwave spectroscopy, spectral modeling, and quantum chemistry
Articles in the same Issue
- Frontmatter
- Reviews
- A computational study of the SNAr reaction of 2-ethoxy-3,5-dinitropyridine and 2-methoxy-3,5-dinitropyridine with piperidine
- Review of research of nanocomposites based on graphene quantum dots
- Atomistic insight into the significantly enhanced photovoltaic cells of monolayer GaTe2 via two-dimensional van der Waals heterostructures engineering
- Mechanistic insight into the interactions between thiazolidinedione derivatives and PTP-1B combining 3D QSAR and molecular docking in the treatment of type 2 diabetes
- Structural and spectroscopic properties of 3-halogenobenzaldehydes: DFT and TDDFT simulations
- Understanding (coupled) large amplitude motions: the interplay of microwave spectroscopy, spectral modeling, and quantum chemistry
