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.

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 / Hidalgo-Figueroa, Sergio*; Estrada-Soto, Samuel; Ramírez-Espinosa, Juan José; Paoli, Paolo; Lori, Giulia; León-Rivera, Ismael; Navarrete-Vázquez, Gabriel. - In: BIOMÉDECINE & PHARMACOTHÉRAPIE. - ISSN 0753-3322. - ELETTRONICO. - 107:(2018), pp. 1302-1310. [10.1016/j.biopha.2018.08.124]

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

Paoli, Paolo;Lori, Giulia;
2018

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.
2018
107
1302
1310
Hidalgo-Figueroa, Sergio*; Estrada-Soto, Samuel; Ramírez-Espinosa, Juan José; Paoli, Paolo; Lori, Giulia; León-Rivera, Ismael; Navarrete-Vázquez, Gabriel
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1138903
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