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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.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2018 Nov; Vol. 107, pp. 1302-1310. Date of Electronic Publication: 2018 Aug 29. - Publication Year :
- 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 IC <subscript>50</subscript> = 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.<br /> (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Animals
Computer Simulation
Dose-Response Relationship, Drug
Escherichia coli enzymology
Hypoglycemic Agents chemistry
Male
Molecular Docking Simulation
Rats, Wistar
Streptozocin
Thiazolidinediones chemistry
Diabetes Mellitus, Experimental drug therapy
Diabetes Mellitus, Type 2 drug therapy
Hypoglycemic Agents chemical synthesis
Hypoglycemic Agents therapeutic use
Protein Tyrosine Phosphatase, Non-Receptor Type 1 antagonists & inhibitors
Thiazolidinediones chemical synthesis
Thiazolidinediones therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 107
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 30257345
- Full Text :
- https://doi.org/10.1016/j.biopha.2018.08.124