Synthesis and evaluation of thiazolidine-2,4-dione/benzazole derivatives as inhibitors of protein tyrosine phosphatase 1B (PTP-1B): Antihyperglycemic activity with molecular docking study - 20/09/18
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Graphical abstract |
Highlights |
• | Thiazolidine-2,4-dione derivatives possess important PTP-1B inhibitory activity. |
• | Compound 1 showed in vivo antihyperglycemic effect. |
• | Molecular docking results indicate that compound 1 bind toward catalytic site of PTP-1B blocking the enzyme activity. |
Abstract |
This work presents the synthesis of two hybrid compounds (1 and 2) with thiazolidine-2,4-dione structure as a central scaffold which were further screened in combo (in vitro as PTP-1B inhibitors, in vivo antihyperglycemic activity, in silico toxicological profile and molecular docking). Compound 1 was tested in the enzymatic assay showing an IC50 = 9.6 ± 0.5 μM and compound 2 showed about a 50% of inhibition of PTP-1B at 20 μM. Therefore, compound 1 was chosen to test its antihyperglycemic effect in a rat model for non-insulin-dependent diabetes mellitus (NIDDM), which was determined at 50 mg/kg in a single dose. The results indicated that compound showed a significant decrease of plasma glucose levels that reached 34%, after a 7 h post-administration. Molecular docking was employed to study the inhibitory properties of thiazolidine-2,4-dione derivatives against Protein Tyrosine Phosphatase 1B (PDB ID: 1c83). Concerning to the two binding sites in this enzyme (sites A and B), compound 1 has shown the best docking score, which indicates the highest affinity. Finally, compounds 1 and 2 have demonstrated an in silico satisfactory pharmacokinetic profile. This shows that it could be a very good candidate or leader for new series of compounds with this central scaffold.
El texto completo de este artículo está disponible en PDF.Keywords : Thiazolidine-2,4-dione, Antihyperglycemic, Molecular docking, PTP-1B
Esquema
Vol 107
P. 1302-1310 - novembre 2018 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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